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Sample records for affecting drug release

  1. Parameters affecting drug release from inert matrices. 1: Monte Carlo simulation.

    PubMed

    Villalobos, Rafael; Viquez, Hugo; Hernández, Beatriz; Ganem, Adriana; Melgoza, Luz María; Young, Paul M

    2012-01-01

    This study investigates the use of Monte Carlo simulation for the determination of release properties from cubic inert matrices. Specifically, the study has focused on factors including porosity, surface area and tortuosity. The release platform was formed by simulating matrices with different ratios of drug and excipient, which undergo drug release in a uni-directional (two-face) or omni-directional (six-face) process. Upon completion of each simulation the matrix 'carcass' was examined and porosity and tortuosity of the medium evaluated. The tortuosity of the medium was evaluated directly by a blind random walk algorithm. These parameters as well as the release profile were then studied with respect to common mathematical models describing drug diffusion (the square-root, power and Weibull models). It was found that, depending on their composition, the matrices systems were either homogeneous or heterogeneous in nature. Furthermore, it was found that the physical parameters could be successfully fitted to the a and b constants of the Weibull model. This approach allows the prediction of drug release from an inert matrix system with the knowledge of a few physical parameters.

  2. What Affects Reintegration of Female Drug Users after Prison Release? Results of a European Follow-Up Study

    ERIC Educational Resources Information Center

    Zurhold, Heike; Moskalewicz, Jacek; Sanclemente, Cristina; Schmied, Gabriele; Shewan, David; Verthein, Uwe

    2011-01-01

    The main objective of this follow-up study is to explore factors influencing the success or failure of women in reintegrating after their release from prison. Female drug users in five European cities were tracked after being released from prison. Out of 234 female prisoners contacted in prisons, 59 were included in the follow-up study. Structured…

  3. Drugs affecting the eye.

    PubMed

    Taylor, F

    1985-08-01

    This discussion reviews drugs that affect the eye, including antihyperglycemic agents; corticosteroids; antirheumatic drugs (quinolines, indomethacin, and allopurinol); psychiatric drugs (phenothiazine, thioridazine, and chlorpromazine); drugs used in cardiology (practolol, amiodarone, and digitalis gylcosides); drugs implicated in optic neuritis and atrophy, drugs with an anticholinergic action; oral contraceptives (OCs); and topical drugs and systemic effects. Refractive changes, either myopic or hypermetropic, can occur as a result of hyperglycemia, and variation in vision is sometimes a presenting symptom in diabetes mellitus. If it causes a change in the refraction, treatment of hyperglycemia almost always produces a temporary hypermetropia. A return to the original refractive state often takes weeks, sometimes months. There is some evidence that patients adequately treated with insulin improve more rapidly than those taking oral medication. Such patients always should be referred for opthalmological evaluation as other factors might be responsible, but it might not be possible to order the appropriate spectacle correction for some time. The most important ocular side effect of the systemic adiministration of corticosteroids is the formation of a posterior subcapsular cataract. Glaucoma also can result from corticosteroids, most often when they are applied topically. Corticosteroids have been implicated in the production of benign intracranial hypertension, which is paradoxical because they also are used in its treatment. The most important side effect of drugs such as chloroquine and hydroxychloroquine is an almost always irreversible maculopathy with resultant loss of central vision. Corneal and retinal changes similar to those caused by the quinolines have been reported with indomethacin, but there is some question about a cause and effect relationship. The National Registry of Drug Induced Ocular Side Effects in the US published 30 case histories of

  4. Metabolically active extracellular vesicles released from hepatocytes under drug-induced liver-damaging conditions modify serum metabolome and might affect different pathophysiological processes.

    PubMed

    Royo, Felix; Palomo, Laura; Mleczko, Justyna; Gonzalez, Esperanza; Alonso, Cristina; Martínez, Ibon; Pérez-Cormenzana, Miriam; Castro, Azucena; Falcon-Perez, Juan M

    2017-02-15

    Hepatocytes are involved in the endogenous and drug metabolism; many of the enzymes involved in those processes are incorporated into extracellular vesicles and secreted into the bloodstream. Liver-damaging conditions modify the molecular cargo of those vesicles significantly. However, no information about the effect of these hepatic vesicles on the extracellular environment is available. Drug-induced liver damage increases the number of circulating extracellular vesicles and affects the release and content of hepatocyte-derived vesicles. In this work, we evaluated the metabolic effect of these vesicles on the composition of the serum. We performed a targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) metabolomics analysis of serum samples. The samples had been first incubated with hepatic extracellular vesicles from hepatocytes challenged with acetaminophen or diclofenac. The incubation affected the serum levels of 67 metabolites, such as amino acids and different species of lipids. The metabolites included various species of phosphatidylcholines and phosphatidylethanolamines. These compounds are the components of biological membranes; our observations suggest that the vesicles might take part in remodelling and maintenance of the membranes. Alterations in the levels of some other serum metabolites might have deleterious consequences, for example, the tetracosanoic acid with its cardiovascular effects. However, some of the metabolites whose levels were increased, including alpha-linoleic and tauroursodeoxycholic acids, have been reported to have a protective effect. Our targeted metabolomics analysis indicated that the hepatic extracellular vesicles act as nano-metabolic machines supplying the extracellular environment with the means to integrate diverse tissue responses. In conclusion, we show that the hepatic extracellular vesicles are metabolically active and might play a role in the physiopathological response to hepatic insults

  5. Design of calcium phosphate ceramics for drug delivery applications in bone diseases: A review of the parameters affecting the loading and release of the therapeutic substance.

    PubMed

    Parent, Marianne; Baradari, Hiva; Champion, Eric; Damia, Chantal; Viana-Trecant, Marylène

    2017-02-21

    Effective treatment of critical-size defects is a key challenge in restorative surgery of bone. The strategy covers the implantation of biocompatible, osteoconductive, bioactive and biodegradable devices which (1) well interact with native tissue, mimic multi-dimensional and hierarchical structure of bone and (2) are able to enhance bone repair, treating post implantation pathologies or bone diseases by local delivery of therapeutic agents. Among different options, calcium phosphate biomaterials are found to be attractive choices, due to their excellent biocompatibility, customisable bioactivity and biodegradability. Several approaches have been established to enhance this material ability to be loaded with a therapeutic agent, in order to obtain an in situ controlled release that meets the clinical needs. This article reviews the most important factors influencing on both drug loading and release capacity of porous calcium phosphate bone substitutes. Characteristics of the carrier, drug/carrier interactions, experimental conditions of drug loading and evaluation of drug delivery are considered successively.

  6. Controlled Drug Release from Pharmaceutical Nanocarriers

    PubMed Central

    Lee, Jinhyun Hannah; Yeo, Yoon

    2014-01-01

    Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics. PMID:25684779

  7. Characterization of Release Mechanism in Polymeric Drug Delivery Systems

    NASA Astrophysics Data System (ADS)

    Laplante, Arthur James; Plachy, Robin Marie; Aou, Kaoru; Ferguson, Jake; Hsu, Shaw Ling

    2006-03-01

    Our polymeric drug delivery system is based on our understanding of phase behavior of polymers [e.g poly(lactic acid)], low molecular drugs and various solvents used in processing. Clearly the different morphologies achieved, based on different phase separation kinetics, can affect drug release rates. Release of drugs, in most cases, involves the exchange between the extraction media and drug. We have characterized the transport behavior using a number of unique techniques. Reflectance infrared spectroscopy has given us a detailed description of the release rate of drugs into the extraction media. Surface plasmon resonance has shown the overall mass loss. UV-visible spectroscopy has yielded the concentration of drug in the solution. These measurements are compared to the release mechanism based on Fickian diffusion. The two step release rates observed can only be explained by taking into account differences in the morphological features of the phase separated films.

  8. Drug release behavior from nanoporous anodic aluminum oxide.

    PubMed

    Kwak, Dae-Hyun; Yoo, Ji-Beom; Kim, Deug Joong

    2010-01-01

    In this study, we developed a new drug delivery system using anodic oxidation. The growth of a porous oxide layer on aluminum under anodic bias in various electrolytes has been studied for more than 40 years. Anodic Aluminum Oxide (AAO) has many uniform nanopores on its surface. This nanoporous surface can be used for drug storage. The effects of the diameter and depth of the AAO on the release characteristics of a drug were investigated. Paclitaxel was used for the drug loading and release test. Paclitaxel was loaded on the inside of the AAO by ultrasonication. The amount of the drug released from the AAO was analyzed by high performance liquid chromatography (HPLC). The pore size did not affect the drug release behavior. However, the depth of the pores had a significant influence on the release rate of the drug.

  9. Fabrication of drug eluting implants: study of drug release mechanism from titanium dioxide nanotubes

    NASA Astrophysics Data System (ADS)

    Hamlekhan, Azhang; Sinha-Ray, Suman; Takoudis, Christos; Mathew, Mathew T.; Sukotjo, Cortino; Yarin, Alexander L.; Shokuhfar, Tolou

    2015-06-01

    Formation of titanium dioxide nanotubes (TNTs) on a titanium surface holds great potential for promoting desirable cellular response. However, prolongation of drug release from these nano-reservoirs remains to be a challenge. In our previous work TNTs were successfully loaded with a drug. In this study the effect of TNTs dimensions on prolongation of drug release is quantified aiming at the introduction of a simple novel technique which overcomes complications of previously introduced methods. Different groups of TNTs with different lengths and diameters are fabricated. Samples are loaded with a model drug and rate of drug release over time is monitored. The relation of the drug release rate to the TNT dimensions (diameter, length, aspect ratio and volume) is established. The results show that an increase in any of these parameters increases the duration of the release process. However, the strongest parameter affecting the drug release is the aspect ratio. In fact, TNTs with higher aspect ratios release drug slower. It is revealed that drug release from TNT is a diffusion-limited process. Assuming that diffusion of drug in (Phosphate-Buffered Saline) PBS follows one-dimensional Fick’s law, the theoretical predictions for drug release profile is compatible with our experimental data for release from a single TNT.

  10. Drug release mechanisms of compressed lipid implants.

    PubMed

    Kreye, F; Siepmann, F; Siepmann, J

    2011-02-14

    The aim of this study was to elucidate the mass transport mechanisms controlling drug release from compressed lipid implants. The latter steadily gain in importance as parenteral controlled release dosage forms, especially for acid-labile drugs. A variety of lipid powders were blended with theophylline and propranolol hydrochloride as sparingly and freely water-soluble model drugs. Cylindrical implants were prepared by direct compression and thoroughly characterized before and after exposure to phosphate buffer pH 7.4. Based on the experimental results, an appropriate mathematical theory was identified in order to quantitatively describe the resulting drug release patterns. Importantly, broad release spectra and release periods ranging from 1 d to several weeks could easily be achieved by varying the type of lipid, irrespective of the type of drug. Interestingly, diffusion with constant diffusivities was found to be the dominant mass transport mechanism, if the amount of water within the implant was sufficient to dissolve all of the drug. In these cases an analytical solution of Fick's second law could successfully describe the experimentally measured theophylline and propranolol hydrochloride release profiles, even if varying formulation and processing parameters, e.g. the type of lipid, initial drug loading, drug particles size as well as compression force and time. However, based on the available data it was not possible to distinguish between drug diffusion control and water diffusion control. The obtained new knowledge can nevertheless significantly help facilitating the optimization of this type of advanced drug delivery systems, in particular if long release periods are targeted, which require time consuming experimental trials.

  11. Electrospinning nanofibers for controlled drug release

    NASA Astrophysics Data System (ADS)

    Banik, Indrani

    Electrospinning is the most widely studied technique for the synthesis of nanofibers. Electrospinning is considered as one of the technologies that can produce nanosized drugs incorporated in polymeric nanofibers. In vitro and in vivo studies have demonstrated that the release rates of drugs from these nanofiber formulations are enhanced compared to those from original drug substance. This technology has the potential for enhancing the oral delivery of poorly soluble drugs. The electrospun mats were made using Polycaprolactone/PCL, Poly(DL-lactide)/PDL 05 and Poly(DL-lactide-co-glycolide)/PLGA. The drugs incorporated in the electrospun fibers were 5-Fluorouracil and Rapamycin. The evidence of the drugs being embedded in the polymers was obtained by scanning electron microscopy (SEM), Raman and infrared spectroscopy. The release of 5-Fluorouracil and Rapamycin were followed by UV-VIS spectroscopy.

  12. Drug Release from Electric Field Responsive Nanoparticles

    PubMed Central

    Ge, Jun; Neofytou, Evgenios; Cahill, Thomas J.; Beygui, Ramin E.; Zare, Richard N.

    2012-01-01

    We describe a new temperature and electric field dual-stimulus responsive nanoparticle system for programmed drug delivery. Nanoparticles of a conducting polymer (polypyrrole) are loaded with therapeutic pharmaceuticals and are subcutaneously localized in vivo with the assistance of a temperature-sensitive hydrogel (PLGA-PEG-PLGA). We have shown that drug release from the conductive nanoparticles is controlled by the application of a weak, external DC electric field. This approach represents a novel interactive drug delivery system that can show an externally tailored release profile with an excellent spatial, temporal, and dosage control. PMID:22111891

  13. Dual drug release from hydrogels covalently containing polymeric micelles that possess different drug release properties.

    PubMed

    Murata, Mari; Uchida, Yusuke; Takami, Taku; Ito, Tomoki; Anzai, Ryosuke; Sonotaki, Seiichi; Murakami, Yoshihiko

    2017-02-09

    In the present study, we designed hydrogels for dual drug release: the hydrogels that covalently contained the polymeric micelles that possess different drug release properties. The hydrogels that were formed from polymeric micelles possessing a tightly packed (i.e., well-entangled) inner core exhibited a higher storage modulus than the hydrogels that were formed from the polymeric micelles possessing a loosely packed structure. Furthermore, we conducted release experiments and fluorescent observations to evaluate the profiles depicting the release of two compounds, rhodamine B and auramine O, from either polymeric micelles or hydrogels. According to our results, (1) hydrogels that covalently contains polymeric micelles that possess different drug release properties successfully exhibit the independent release behaviors of the two compounds and (2) fluorescence microscopy can greatly facilitate efforts to evaluate drug release properties of materials.

  14. Controlled drug release from bifunctionalized mesoporous silica

    SciTech Connect

    Xu Wujun; Gao Qiang; Xu Yao Wu Dong; Sun Yuhan; Shen Wanling; Deng Feng

    2008-10-15

    Serial of trimethylsilyl-carboxyl bifunctionalized SBA-15 (TMS/COOH/SBA-15) have been studied as carriers for controlled release of drug famotidine (Famo). To load Famo with large capacity, SBA-15 with high content of carboxyl groups was successfully synthesized by one-pot synthesis under the assistance of KCl. The mesostructure of carboxyl functionalized SBA-15 (COOH/SBA-15) could still be kept even though the content of carboxyl groups was up to 57.2%. Increasing carboxyl content could effectively enhance the loading capacity of Famo. Compared with pure SBA-15, into which Famo could be hardly adsorbed, the largest drug loading capacity of COOH/SBA-15 could achieve 396.9 mg/g. The release of Famo from mesoporous silica was studied in simulated intestine fluid (SIF, pH=7.4). For COOH/SBA-15, the release rate of Famo decreased with narrowing pore size. After grafting TMS groups on the surface of COOH/SBA-15 with hexamethyldisilazane, the release of Famo was greatly delayed with the increasing content of TMS groups. - Graphical abstract: Trimethylsilyl-carboxyl bifunctionalized SBA-15 has been studied as carrier for controlled release of drug famotidine. To load drug with large capacity, SBA-15 with high content of carboxyl groups was successfully synthesized. After grafting trimethylsilyl groups on the surface of carboxyl functionalized SBA-15, the release of Famo was greatly delayed with the increasing content of TMS groups.

  15. Phasic dopamine release in appetitive behaviors and drug abuse

    PubMed Central

    Wanat, Matthew J.; Willuhn, Ingo; Clark, Jeremy J.; Phillips, Paul E. M.

    2010-01-01

    Short phasic bursts of neuronal activity in dopamine neurons produce rapid and transient increases in extracellular dopamine concentrations throughout the mesocorticolimbic system, which are associated with the initiation of goal-directed behaviors. It is well established that acute exposure to many addictive drugs produce increases in tonic dopamine levels that occur on the order of minutes. However, recent studies suggest that abused drugs similarly enhance phasic dopamine release events that occur on a subsecond time scale. Furthermore, drug experience modulates the synaptic and intrinsic properties of dopamine neurons, which could affect dopamine burst firing and phasic dopamine release. This review will provide a general introduction to the mesolimbic dopamine system, as well as the primary methods used to detect dopamine neurons and dopamine release. We present the role of phasic dopamine release in appetitive behaviors in the context of contemporary theories regarding the function of dopamine. Next we discuss the known drug-induced changes to dopamine neurons and phasic release in both in vitro and in vivo preparations. Finally, we offer a simple model that chronic drug experience attenuates tonic/basal dopamine levels but promotes phasic dopamine release, which may result in aberrant goal-directed behaviors contributing to the development of addiction. PMID:19630749

  16. Infuence of Microstructure in Drug Release Behavior of Silica Nanocapsules

    PubMed Central

    Zoltan, Tamara

    2013-01-01

    Meso- and nanoporous structures are adequate matrices for controlled drug delivery systems, due to their large surface areas and to their bioactive and biocompatibility properties. Mesoporous materials of type SBA-15, synthesized under different pH conditions, and zeolite beta were studied in order to compare the different intrinsic morphological characteristics as pore size, pore connectivity, and pore geometry on the drug loading and release process. These materials were characterized by X-ray diffraction, nitrogen adsorption, scanning and transmission electron microscopy, and calorimetric measurements. Ibuprofen (IBU) was chosen as a model drug for the formulation of controlled-release dosage forms; it was impregnated into these two types of materials by a soaking procedure during different periods. Drug loading and release studies were followed by UV-Vis spectrophotometry. All nano- and mesostructured materials showed a similar loading behavior. It was found that the pore size and Al content strongly influenced the release process. These results suggest that the framework structure and architecture affect the drug adsorption and release properties of these materials. Both materials offer a good potential for a controlled delivery system of ibuprofen. PMID:23986870

  17. Recommended for release on recognizance: factors affecting pretrial release recommendations.

    PubMed

    Petee, T A

    1994-06-01

    Researchers have acknowledged the influence of pretrial release agencies in judicial decision making regarding bail; however, few researchers have focused on the process used by the pretrial release agencies to make bail-bond recommendations. In this study I sought to establish which factors were most salient in making the decision to recommend a defendant for release on recognizance. I found that both officially sanctioned release criteria and "extralegal" variables were predictive of this decision.

  18. Understanding controlled drug release from mesoporous silicates: theory and experiment.

    PubMed

    Ukmar, T; Maver, U; Planinšek, O; Kaučič, V; Gaberšček, M; Godec, A

    2011-11-07

    Based on the results of carefully designed experiments upgraded with appropriate theoretical modeling, we present clear evidence that the release curves from mesoporous materials are significantly affected by drug-matrix interactions. In experimental curves, these interactions are manifested as a non-convergence at long times and an inverse dependence of release kinetics on pore size. Neither of these phenomena is expected in non-interacting systems. Although both phenomena have, rather sporadically, been observed in previous research, they have not been explained in terms of a general and consistent theoretical model. The concept is demonstrated on a model drug indomethacin embedded into SBA-15 and MCM-41 porous silicates. The experimental release curves agree exceptionally well with theoretical predictions in the case of significant drug-wall attractions. The latter are described using a 2D Fokker-Planck equation. One could say that the interactions affect the relative cross-section of pores where the local flux has a non-vanishing axial component and in turn control the effective transfer of drug into bulk solution. Finally, we identify the critical parameters determining the pore size dependence of release kinetics and construct a dynamic phase diagram of the various resulting transport regimes.

  19. Drug releasing systems in cardiovascular tissue engineering.

    PubMed

    Spadaccio, Cristiano; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto; Toyoda, Yoshiya; Genovese, Jorge A

    2009-03-01

    Heart disease and atherosclerosis are the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts; however, current artificial grafts carry significant limitations, including thrombosis, infection, limited durability and the inability to grow. Tissue engineering of blood vessels, cardiovascular structures and whole organs is a promising approach for creating replacement tissues to repair congenital defects and/or diseased tissues. In an attempt to surmount the shortcomings of artificial grafts, tissue-engineered cardiovascular graft (TECVG), constructs obtained using cultured autologous vascular cells seeded onto a synthetic biodegradable polymer scaffold, have been developed. Autologous TECVGs have the potential advantages of growth, durability, resistance to infection, and freedom from problems of rejection, thrombogenicity and donor scarcity. Moreover polymers engrafted with growth factors, cytokines, drugs have been developed allowing drug-releasing systems capable of focused and localized delivery of molecules depending on the environmental requirements and the milieu in which the scaffold is placed. A broad range of applications for compound-releasing, tissue-engineered grafts have been suggested ranging from drug delivery to gene therapy. This review will describe advances in the development of drug-delivery systems for cardiovascular applications focusing on the manufacturing techniques and on the compounds delivered by these systems to date.

  20. Drug releasing systems in cardiovascular tissue engineering

    PubMed Central

    Spadaccio, Cristiano; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto; Toyoda, Yoshiya; Genovese, Jorge A

    2009-01-01

    Abstract Heart disease and atherosclerosis are the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts; however, current artificial grafts carry significant limitations, including thrombosis, infection, limited durability and the inability to grow. Tissue engineering of blood vessels, cardiovascular structures and whole organs is a promising approach for creating replacement tissues to repair congenital defects and/or diseased tissues. In an attempt to surmount the shortcomings of artificial grafts, tissue-engineered cardiovascular graft (TECVG), constructs obtained using cultured autologous vascular cells seeded onto a synthetic biodegradable polymer scaffold, have been developed. Autologous TECVGs have the potential advantages of growth, durability, resistance to infection, and freedom from problems of rejection, thrombogenicity and donor scarcity. Moreover polymers engrafted with growth factors, cytokines, drugs have been developed allowing drug-releasing systems capable of focused and localized delivery of molecules depending on the environmental requirements and the milieu in which the scaffold is placed. A broad range of applications for compound-releasing, tissue-engineered grafts have been suggested ranging from drug delivery to gene therapy. This review will describe advances in the development of drug-delivery systems for cardiovascular applications focusing on the manufacturing techniques and on the compounds delivered by these systems to date. PMID:19379142

  1. Evaluation of the drug solubility and rush ageing on drug release performance of various model drugs from the modified release polyethylene oxide matrix tablets.

    PubMed

    Shojaee, Saeed; Nokhodchi, Ali; Maniruzzaman, Mohammed

    2017-02-01

    Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide. Both polyox matrices 750 and 303 grade were used as model carriers for the manufacture of tablets stored at 40 °C. The results of the present study suggest that the drug release from the matrix was affected by the length of storage conditions, solubility of drugs and the molecular weight of the polymers. Generally, increased drug release rates were prevalent in soluble drug formulations (propranolol) when stored at the elevated temperature (40 °C). In contrast, it was not observed with semi soluble (theophylline) and poorly soluble (zonisamide) drugs especially when formulated with PEO 303 polymer. This indicates that the main parameters controlling the drug release from fresh polyox matrices are the solubility of the drug in the dissolution medium and the molecular weight of the polymer. DSC traces indicated that that there was a big difference in the enthalpy and melting points of fresh and aged PEO samples containing propranolol, whereas the melting point of the aged polyox samples containing theophylline and zonisamide was unaffected. Graphical abstract ᅟ.

  2. How Do Beta Blocker Drugs Affect Exercise?

    MedlinePlus

    ... Aneurysm More How do beta blocker drugs affect exercise? Updated:Aug 5,2015 Beta blockers are a ... about them: Do they affect your ability to exercise? The answer can vary a great deal, depending ...

  3. Double-Layered Matrix of Shellac Wax-Lutrol in Controlled Dual Drug Release.

    PubMed

    Phaechamud, Thawatchai; Choncheewa, Chai-Ek

    2016-12-01

    Double-layered matrix tablets prepared from shellac wax-lutrol were fabricated using a molding technique, and the release of hydrochlorothiazide and propranolol HCl from the inner tablet or outer layer was studied. The simultaneous determination of dual drug release was measured with first derivative UV spectrophotometry. The tablet containing shellac wax as the outer tablet and lutrol as the inner tablet showed more appropriate drug release and the size of the inner layer influenced the rate of drug release. In addition, the aqueous solubility of the drug and the components of the inner tablet or outer layer affected the drug release behavior. Most of the double-layered tablets exhibited the drug-release pattern which fitted well with zero-order kinetic due to the restriction of the release surface. Biphasic drug release pattern was found in the tablet of which the outer layer rapidly eroded. The drug dissolution data from drug-loaded-outer layer could predict the dissolution time for the outer layer of drug-loaded inner part of double-layered matrix tablet. Incorporation of lutrol increased the drug release from shellac wax matrix, and the zero-order release was attained by fabricating it into a double-layered tablet.

  4. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Dissolution and drug release testing. 343.90 Section 343.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INTERNAL ANALGESIC, ANTIPYRETIC, AND ANTIRHEUMATIC DRUG PRODUCTS FOR...

  5. Modeling of drug release from bulk-degrading polymers.

    PubMed

    Lao, Luciana Lisa; Peppas, Nicholas A; Boey, Freddy Yin Chiang; Venkatraman, Subbu S

    2011-10-10

    This paper aims to provide a comprehensive review of the various models or simulations for predicting drug release from bulk-degrading systems. A brief description of bulk degradation processes and factors affecting the degradation rate, and consequently the release kinetics, is presented first. Next, several important classical models, often used as the basis for subsequent model development, are discussed. Both mathematical models and Monte-Carlo based simulations have been developed for controlled release from bulk-degrading systems. The mathematical models can be further subdivided into two categories. First, the diffusion-based models whose transport mechanism is mainly governed by diffusion, but with degradation-dependent diffusion coefficients. These are generally simpler and easier to use and are sufficient to illustrate mono-phasic release. Second, comprehensive models that combine diffusion with other theories such as erosion, drug dissolution and/or pore percolations. These models usually involve more complex equations but provide good matches for multi-phasic release profiles.

  6. Controlled release of an anti-cancer drug from DNA structured nano-films

    NASA Astrophysics Data System (ADS)

    Cho, Younghyun; Lee, Jong Bum; Hong, Jinkee

    2014-02-01

    We demonstrate the generation of systemically releasable anti-cancer drugs from multilayer nanofilms. Nanofilms designed to drug release profiles in programmable fashion are promising new and alternative way for drug delivery. For the nanofilm structure, we synthesized various unique 3-dimensional anti cancer drug incorporated DNA origami structures (hairpin, Y, and X shaped) and assembled with peptide via layer-by-layer (LbL) deposition method. The key to the successful application of these nanofilms requires a novel approach of the influence of DNA architecture for the drug release from functional nano-sized surface. Herein, we have taken first steps in building and controlling the drug incorporated DNA origami based multilayered nanostructure. Our finding highlights the novel and unique drug release character of LbL systems in serum condition taken full advantages of DNA origami structure. This multilayer thin film dramatically affects not only the release profiles but also the structure stability in protein rich serum condition.

  7. Development of metoprolol tartrate-loaded sustained-release pellets: effect of talc on the mechanism of drug release.

    PubMed

    Wang, Yuli; Yang, Meiyan; Shen, Ruifang; Shao, Shuai; Chen, Lu; Gong, Wei; Shan, Li; Gao, Chunsheng

    2016-07-28

    Talc is one of the most commonly used antiadherents in the coating film. However, the mechanism of influence of talc on drug release has yet to be fully understood. In this study, metoprolol tartrate (MT)-loaded Eudragit NE 30 D-coated sustained-release (SR) pellets were prepared using talc as an antiadherent in the layering and coating processes. Talc significantly reduced the stickiness of the layered or coated substrates, thus enhancing the process smoothness. Moreover, the incorporation of talc into the coating film significantly affected drug release. The water vapor permeability and drug permeability of free films increased as the concentration of talc increased. Importantly, talc had a dynamic effect on the drug release. The drug release rate of the pellets in the initial stage (within 2 h) increased with increasing talc concentrations, which exceeded the critical pigment volume concentration resulted in leaks formation in the coated film. However, subsequent swelling of the membrane and expansion of the copolymer network eliminated the influence of talc and the drug release was then controlled by the polymeric membrane. These results suggest that talc contributed to the reduction of the sticking of layered or coated substrates, and facilitated the manufacturing process and drug release properties.

  8. SU-F-19A-08: Optimal Time Release Schedule of In-Situ Drug Release During Permanent Prostate Brachytherapy

    SciTech Connect

    Cormack, R; Ngwa, W; Makrigiorgos, G; Tangutoori, S; Rajiv, K; Sridhar, S

    2014-06-15

    Purpose: Permanent prostate brachytherapy spacers can be used to deliver sustained doses of radiosentitizing drug directly to the target, in order to enhance the radiation effect. Implantable nanoplatforms for chemo-radiation therapy (INCeRTs) have a maximum drug capacity and can be engineered to control the drug release schedule. The optimal schedule for sensitization during continuous low dose rate irradiation is unknown. This work studies the optimal release schedule of drug for both traditional sensitizers, and those that work by suppressing DNA repair processes. Methods: Six brachytherapy treatment plans were used to model the anatomy, implant geometry and calculate the spatial distribution of radiation dose and drug concentrations for a range of drug diffusion parameters. Three state partial differential equations (cells healthy, damaged or dead) modeled the effect of continuous radiation (radiosensitivities α,β) and cellular repair (time tr) on a cell population. Radiosensitization was modeled as concentration dependent change in α,β or tr which with variable duration under the constraint of fixed total drug release. Average cell kill was used to measure effectiveness. Sensitization by means of both enhanced damage and reduced repair were studied. Results: Optimal release duration is dependent on the concentration of radiosensitizer compared to the saturation concentration (csat) above which additional sensitization does not occur. Long duration drug release when enhancing α or β maximizes cell death when drug concentrations are generally over csat. Short term release is optimal for concentrations below saturation. Sensitization by suppressing repair has a similar though less distinct trend that is more affected by the radiation dose distribution. Conclusion: Models of sustained local radiosensitization show potential to increase the effectiveness of radiation in permanent prostate brachytherapy. INCeRTs with high drug capacity produce the greatest

  9. Polymer micelles for delayed release of therapeutics from drug-releasing surfaces with nanotubular structures.

    PubMed

    Sinn Aw, Moom; Addai-Mensah, Jonas; Losic, Dusan

    2012-08-01

    A new approach to engineer a local drug delivery system with delayed release using nanostructured surface with nanotube arrays is presented. TNT arrays electrochemically generated on a titanium surface are used as a model substrate. Polymer micelles as drug carriers encapsulated with drug are loaded at the bottom of the TNT structure and their delayed release is obtained by loading blank micelles (without drug) on the top. The delayed and time-controlled drug release is successfully demonstrated by controlling the ratio of blank and drug loaded-micelles. The concept is verified using four different polymer micelles (regular and inverted) loaded with water-insoluble (indomethacin) and water-soluble drugs (gentamicin).

  10. Programmable and on-demand drug release using electrical stimulation

    PubMed Central

    Yi, Y. T.; Sun, J. Y.; Lu, Y. W.; Liao, Y. C.

    2015-01-01

    Recent advancement in microfabrication has enabled the implementation of implantable drug delivery devices with precise drug administration and fast release rates at specific locations. This article presents a membrane-based drug delivery device, which can be electrically stimulated to release drugs on demand with a fast release rate. Hydrogels with ionic model drugs are sealed in a cylindrical reservoir with a separation membrane. Electrokinetic forces are then utilized to drive ionic drug molecules from the hydrogels into surrounding bulk solutions. The drug release profiles of a model drug show that release rates from the device can be electrically controlled by adjusting the stimulated voltage. When a square voltage wave is applied, the device can be quickly switched between on and off to achieve pulsatile release. The drug dose released is then determined by the duration and amplitude of the applied voltages. In addition, successive on/off cycles can be programmed in the voltage waveforms to generate consistent and repeatable drug release pulses for on-demand drug delivery. PMID:25825612

  11. Drug loading and release on tumor cells using silk fibroin-albumin nanoparticles as carriers

    NASA Astrophysics Data System (ADS)

    Subia, B.; Kundu, S. C.

    2013-01-01

    Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin-albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin-albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules.

  12. Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs

    NASA Astrophysics Data System (ADS)

    Taepaiboon, Pattama; Rungsardthong, Uracha; Supaphol, Pitt

    2006-05-01

    Mats of PVA nanofibres were successfully prepared by the electrospinning process and were developed as carriers of drugs for a transdermal drug delivery system. Four types of non-steroidal anti-inflammatory drug with varying water solubility property, i.e. sodium salicylate (freely soluble in water), diclofenac sodium (sparingly soluble in water), naproxen (NAP), and indomethacin (IND) (both insoluble in water), were selected as model drugs. The morphological appearance of the drug-loaded electrospun PVA mats depended on the nature of the model drugs. The 1H-nuclear magnetic resonance results confirmed that the electrospinning process did not affect the chemical integrity of the drugs. Thermal properties of the drug-loaded electrospun PVA mats were analysed by differential scanning calorimetry and thermogravimetric analysis. The molecular weight of the model drugs played a major role on both the rate and the total amount of drugs released from the as-prepared drug-loaded electrospun PVA mats, with the rate and the total amount of the drugs released decreasing with increasing molecular weight of the drugs. Lastly, the drug-loaded electrospun PVA mats exhibited much better release characteristics of the model drugs than drug-loaded as-cast films.

  13. Superhydrophobic coating to delay drug release from drug-loaded electrospun fibrous materials

    NASA Astrophysics Data System (ADS)

    Song, Botao; Xu, Shichen; Shi, Suqing; Jia, Pengxiang; Xu, Qing; Hu, Gaoli; Zhang, Hongxin; Wang, Cuiyu

    2015-12-01

    The drug-loaded electrospun fibrous materials showed attractive applications in biomedical fields; however, the serve burst release of drug from this kind of drug carrier limited its further applications. In this study, inspired by water strong repellency of superhydrophobic surface, the drug-loaded electrospun fibrous mat coated with superhydrophobic layer was constructed to retard and control drug release. The results indicated that the superhydrophobic coating could be simply fabricated on the drug-loaded electrospun mat by the electrospray approach, and the thickness of the superhydrophobic coating could be finely controlled by varying the deposition time. It was further found that, as compared with drug-loaded electrospun mats, drug released sustainably from the samples coated with superhydrophobic layer, and the drug release rate could be controlled by the thickness of superhydrophobic layer. In summary, the current approach of coating a superhydrophobic layer on the drug-loaded electrospun fibrous materials offered a fundament for drug sustained release.

  14. Sustain-release of various drugs from leucaena leucocephala polysaccharide.

    PubMed

    Jeevanandham, S; Sekar, M; Dhachinamoorthi, D; Muthukumaran, M; Sriram, N; Joysaruby, J

    2010-01-01

    This study examines the sustained release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water-insoluble (indomethacin) drugs from Leucaena leucocephala seed Gum isolated from Leucaena leucocephala kernel powder. It further investigates the effect of incorporation of diluents like microcrystalline cellulose and lactose on release of caffeine and partial cross-linking of the gum (polysaccharide) on release of acetaminophen. Applying exponential equation, the mechanism of release of soluble drugs was found to be anomalous. The insoluble drug showed near case II or zero-order release mechanism. The rate of release was in the decreasing order of caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in release kinetics of drug was observed on blending with diluents. However, the rate of release varied with type and amount of blend in the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of release of drug decreased on partial cross-linking and the mechanism of release was found to be super case II.

  15. Modified release of coated sugar spheres using drug-containing polymeric dispersions.

    PubMed

    Kim, Tae-Wan; Ji, Chang-Won; Shim, Sang-Young; Lee, Beom-Jin

    2007-01-01

    A drug-containing polymeric dispersion was applied onto nonpareil sugar spheres (18/20 mesh) using a fluid-bed spray coater. Eudragit RS30D was selected as the polymeric coating material. Melatonin secreted by the pineal gland in a circadian rhythm was used as a model drug. The release behaviors of the coated sugar spheres were investigated in gastric fluid (pH 1.4) for 2 h, and then continuously in intestinal fluid (pH 7.4) for 14 h. The release rate of the coated sugar spheres decreased with increasing coating levels. The solvent (ethanol) in the coating dispersions significantly decreased the release of the drug due to the good dispersion of the low solubility melatonin in the polymeric films. The polymer (polyvinylpyrrolidone, PVP) and drug contents in the coating dispersions did not affect the release rate. Most of all, the release profiles were drastically changed according to the type and concentration of plasticizers used. The current coating methods that use drug-containing polymeric dispersions could be useful for simultaneous drug loadings and their modified release. The solubilization and controlled release of poorly water-soluble drugs can be achieved as both the solubilizers and drugs are present in the drug-containing polymeric dispersions.

  16. Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release.

    PubMed

    Yin, Junfa; Cui, Yue; Yang, Gengliang; Wang, Hailin

    2010-11-07

    Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release are fabricated by the combination of template synthesis and ATRP grafting. The release of R-propranolol from the imprinted nanotubes in rats is restricted while the release of pharmacologically active S-enantiomer is greatly promoted.

  17. Development of an injectable two-phase drug delivery system for sequential release of antiresorptive and osteogenic drugs.

    PubMed

    Zou, Y; Brooks, J L; Talwalkar, V; Milbrandt, T A; Puleo, D A

    2012-01-01

    Unlike controlled release systems that deliver a single drug, dual or multidrug delivery systems with distinct release profiles are more likely to promote timely and effective tissue regeneration as they provide both temporally and concentration-dependent release of different molecules to mimic natural biological events. In this study, an injectable and biodegradable delivery system was developed to sequentially release an antiresorptive drug (clodronate) followed by an osteogenic agent (simvastatin) to treat bone disease. The injectable delivery system comprised simvastatin-loaded gelatin microspheres suspended in a viscous solution of carboxymethylcellulose (CMC) containing clodronate. Several factors (CMC concentration, glutaraldehyde concentration, simvastatin loading, and gelatin microsphere processing conditions) were investigated for their effects on drug release. Clodronate release was not affected by CMC concentration, with complete delivery within 12 hr, and simvastatin release could be modulated by cross-linking of the gelatin microspheres, loading, and washing conditions. Burst release of simvastatin was reduced from 70% to 6% in conjunction with sustained release for up to 3 weeks. The combined system showed early release of the antiresorptive clodronate sequentially followed by sustained delivery of the osteogenic simvastatin. This robust and flexible two-phase delivery system may prove useful for applications in which multiple drug delivery is desired.

  18. Drug release from hydrogel: a new understanding of transport phenomena.

    PubMed

    Perale, G; Rossi, F; Santoro, M; Marchetti, P; Mele, A; Castiglione, F; Raffa, E; Masi, M

    2011-06-01

    In tissue engineering, i.e., in combined advanced technologies to replace damaged or missing parts of living tissues, emerging strategies strongly point toward the use of hydrogels also for their ability of being vehicles for local controlled drug delivery. The investigation of drug release mechanisms in such matrices thus plays a key role in the design of smart system but literature is still very controversial on theoretical interpretations and understanding of available data. In this framework we used the new HRMAS-NMR DOSY technique to study the diffusive motions of sodium fluorescein, a drug mimetic small chromophoric molecule, loaded in a promising hydrogel developed for tissue engineering. While fluorescein behavior in water was as expected, also showing aggregation from mid concentrations, data collected within hydrogel samples surprisingly showed no aggregation and diffusion coefficients were always higher with respect to aqueous solution. Furthermore, the promotion of diffusion increased along with fluorescein concentration. The proportion of this effect was directly linked to hydrogel mesh size, thus carrying intrinsic novelty, but also complexity, and suggesting that not only strictly hydrodynamic effects should be considered but also electrostatic interactions between polymer chains and drug molecules might be key players in avoiding fluorescein aggregation and also affecting diffusivity.

  19. Development of a novel 3-month drug releasing risperidone microspheres

    PubMed Central

    Yerragunta, Bhanusree; Jogala, Satheesh; Chinnala, Krishna Mohan; Aukunuru, Jithan

    2015-01-01

    Objective: The purpose of this study was to develop an ideal microsphere formulation of risperidone that would prolong the drug release for 3 months in vivo and avoid the need for co-administration of oral tablets. Materials and Methods: Polycaprolactones (PCL) were used as polymers to prepare microspheres. The research included screening and optimizing of suitable commercial polymers of variable molecular weights: PCL-14000, PCL-45000, PCL-80000 or the blends of these polymers to prepare microspheres with zero-order drug-releasing properties without the lag phase. In the present study, the sustained release risperidone microspheres were prepared by o/w emulsion solvent evaporation technique and the yield was determined. Microspheres were evaluated for their drug content and in vitro drug release. Microspheres prepared using a blend of PCL-45000 and PCL-80000 at a ratio of 1:1 resulted in the release of the drug in a time frame of 90 days, demonstrated zero-order drug release without lag time and burst release. This formulation was considered optimized formulation. Optimized formulation was characterized for solid state of the drug using differential scanning calorimetry, surface morphology using scanning electron microscopy and in vivo drug release in rats. Results: The surface of the optimized formulation was smooth, and the drug changed its physical form in the presence of blends of polymers and upon fabrication of microspheres. The optimized formulation also released the drug in vivo for a period of 90 days. Conclusions: From our study, it was concluded that these optimized microspheres showed great potential for a better depot preparation than the marketed Risperdal Consta™ and, therefore, could further improve patient compliance. PMID:25709335

  20. Alternate polyelectrolyte coating of chitosan beads for extending drug release.

    PubMed

    Srinatha, A; Pandit, Jayanta K

    2008-01-01

    In the present study, we addressed the factors modifying ciprofloxacin release from multiple coated beads. Beads were prepared by simple ionic cross-linking with sodium tripolyphoshate and coated with alginate and/or chitosan to prepare single, double, or multilayered beads. The water uptake capacity depended on the nature of beads (coated or uncoated) and pH of test medium. The number of coatings given to the beads influenced ciprofloxacin release rate. The coating significantly decreased the drug release from the beads in comparison to uncoated beads (p < 0.001). When the beads were given three coatings, viz., alginate, chitosan, and again alginate, the drug release appeared to follow the pattern exhibited by colon-targeted drug delivery systems with time dependent release behavior. The increase in coating formed a barrier for easy ingress of dissolution medium into the bead matrix, reducing the diffusion of drug.

  1. The use of solid lipid nanoparticles for sustained drug release.

    PubMed

    Attama, Anthony A; Umeyor, Chukwuebuka E

    2015-01-01

    Novel solid lipid drug delivery systems such as solid lipid nanoparticles (SLN) have attracted wide and increasing attention in recent years. It has been sought as an interesting alternative drug delivery carrier system for bioactives for a variety of delivery routes. They show major advantages such as sustained release, improved bioavailability, improved drug incorporation and very wide application. This paper presents a discussion on the production protocols of SLN, lyophilization of SLN and delivery of SLN across the blood-brain barrier. Special attention was also paid to entrapment and release of drugs from SLN and strategies to enhance drug entrapment in SLN for sustained release. Analytical methods for the characterization of SLN were also discussed. Various routes of administration of SLN were presented as well as a consideration of the ethical issues and future prospects in the production and use of SLN for sustained release of bioactives.

  2. Investigating the feasibility of temperature-controlled accelerated drug release testing for an intravaginal ring.

    PubMed

    Externbrink, Anna; Clark, Meredith R; Friend, David R; Klein, Sandra

    2013-11-01

    The objective of the present study was to investigate if temperature can be utilized to accelerate drug release from Nuvaring®, a reservoir type intravaginal ring based on polyethylene vinyl acetate copolymer that releases a constant dose of contraceptive steroids over a duration of 3 weeks. The reciprocating holder apparatus (USP 7) was utilized to determine real-time and accelerated etonogestrel release from ring segments. It was demonstrated that drug release increased with increasing temperature which can be attributed to enhanced drug diffusion. An Arrhenius relationship of the zero-order release constants was established, indicating that temperature is a valid parameter to accelerate drug release from this dosage form and that the release mechanism is maintained under these accelerated test conditions. Accelerated release tests are particularly useful for routine quality control to assist during batch release of extended release formulations that typically release the active over several weeks, months or even years, since they can increase the product shelf life. The accelerated method should therefore be able to discriminate between formulations with different release characteristics that can result from normal manufacturing variance. In the case of Nuvaring®, it is well known that the process parameters during the extrusion process strongly influence the polymeric structure. These changes in the polymeric structure can affect the permeability which, in turn, is reflected in the release properties. Results from this study indicate that changes in the polymeric structure can lead to a different temperature dependence of the release rate, and as a consequence, the accelerated method can become less sensitive to detect changes in the release properties. When the accelerated method is utilized during batch release, it is therefore important to take this possible restriction into account and to evaluate the accelerated method with samples from non

  3. Effect of lipolysis on drug release from self-microemulsifying drug delivery systems (SMEDDS) with different core/shell drug location.

    PubMed

    Zhang, Jianbin; Lv, Yan; Zhao, Shan; Wang, Bing; Tan, Mingqian; Xie, Hongguo; Lv, Guojun; Ma, Xiaojun

    2014-06-01

    The objective of this study is to investigate the effect of lipolysis on the release of poorly water-soluble drug from SMEDDS in the perspective of drug core/shell location. For this purpose, four SMEDDS formulations with various core/shell properties were developed based on long-chain lipid or medium-chain lipid as well as different surfactant/oil ratios. Poorly water-soluble drugs, hymecromone and resveratrol, were significantly solubilized in all SMEDDS formulations and the diluted microemulsions. Fluorescence spectra analysis indicated that hymecromone was mainly located in the shell of microemulsions, while resveratrol was located in the core. The effect of lipolysis on the release rates of drugs with different core/shell locations were investigated by a modified in vitro drug release model. For the drug located in the shell, hymecromone, the release profiles were not affected during the lipolysis process and no significant differences were observed among four formulations. For the drug located in the core, resveratrol, the release rates were increased to various degrees depending on the extent of digestion. In conclusion, the drug core/shell location plays an important role for determining the effect of lipolysis on drug release from SMEDDS formulation.

  4. Drug Release and Skin Permeation from Lipid Liquid Crystalline Phases

    NASA Astrophysics Data System (ADS)

    Costa-Balogh, F. O.; Sparr, E.; Sousa, J. J. S.; Pais, A. A. C. C.

    We have studied drug release and skin permeation from several different liquid crystalline lipid formulations that may be used to control the respective release rates. We have studied the release and permeation through human skin of a water-soluble and amphiphilic drug, propranolol hydrochloride, from several formulations prepared with monoolein and phytantriol as permeation enhancers and controlled release excipients. Diolein and cineol were added to selected formulations. We observed that viscosity decreases with drug load, wich is compatible with the occurrence of phase changes. Diolein stabilizes the bicontinuous cubic phases leading to an increase in viscosity and sustained release of the drug. The slowest release was found for the cubic phases with higher viscosity. Studies on skin permeation showed that these latter formulations also presented lower permeability than the less viscous monoolein lamellar phases. Formulations containing cineol originated higher permeability with higher enhancement ratios. Thus, the various formulations are adapted to different circumstances and delivery routes. While a slow release is usually desired for drug sustained delivery, the transdermal route may require a faster release. Lamellar phases, which are less viscous, are more adapted to transdermal applications. Thus, systems involving lamellar phases of monoolein and cineol are good candidates to be used as skin permeation enhancers for propranolol hydrochloride.

  5. Diffuse-interface theory for structure formation and release behavior in controlled drug release systems.

    PubMed

    Saylor, David M; Kim, Chang-Soo; Patwardhan, Dinesh V; Warren, James A

    2007-11-01

    A common method of controlling drug release has been to incorporate the drug into a polymer matrix, thereby creating a diffusion barrier that slows the rate of drug release. It has been demonstrated that the internal microstructure of these drug-polymer composites can significantly impact the drug release rate. However, the effect of processing conditions during manufacture on the composite structure and the subsequent effects on release behavior are not well understood. We have developed a diffuse-interface theory for microstructure evolution that is based on interactions between drug, polymer and solvent species, all of which may be present in either crystalline or amorphous states. Because the theory can be applied to almost any specific combination of material species and over a wide range of environmental conditions, it can be used to elucidate and quantify the relationships between processing, microstructure and release response in controlled drug release systems. Calculations based on the theory have now demonstrated that, for a characteristic delivery system, variations in microstructure arising due to changes in either drug loading or processing time, i.e. evaporation rate, could have a significant impact on both the bulk release kinetics and the uniformity of release across the system. In fact, we observed that changes in process time alone can induce differences in bulk release of almost a factor of two and typical non-uniformities of +/-30% during the initial periods of release. Because these substantial variations may have deleterious clinical ramifications, it is critical that both the system microstructure and the control of that microstructure are considered to ensure the device will be both safe and effective in clinical use.

  6. Effect of Antiadherents on the Physical and Drug Release Properties of Acrylic Polymeric Films.

    PubMed

    Ammar, Hussein O; Ghorab, Mamdouh M; Felton, Linda A; Gad, Shadeed; Fouly, Aya A

    2016-06-01

    Antiadherents are used to decrease tackiness of a polymer coating during both processing and subsequent storage. Despite being a common excipient in coating formulae, antiadherents may affect mechanical properties of the coating film as well as drug release from film-coated tablets, but how could addition of antiadherents affect these properties and to what extent and is there a relation between the physical characteristics of the tablet coat and the drug release mechanisms? The aim of this study was to evaluate physical characteristics of films containing different amounts of the antiadherents talc, glyceryl monostearate, and PlasACRYL(TM) T20. Eudragit RL30D and Eudragit RS30D as sustained release polymers and Eudragit FS30D as a delayed release material were used. Polymer films were characterized by tensile testing, differential scanning calorimetry (DSC), microscopic examination, and water content as calculated from loss on drying. The effect of antiadherents on in vitro drug release for the model acetylsalicylic acid tablets coated with Eudragit FS30D was also determined. Increasing talc concentration was found to decrease the ability of the polymer films to resist mechanical stress. In contrast, glyceryl monostearate (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher than 25% caused negative effects, which make 25% concentration recommended to be used with acrylic polymers. All antiadherents delayed the drug release at all coating levels; hence, different tailoring of drug release may be achieved by adjusting antiadherent concentration with coating level.

  7. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

    NASA Astrophysics Data System (ADS)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  8. Mathematical modeling of drug release from lipid dosage forms.

    PubMed

    Siepmann, J; Siepmann, F

    2011-10-10

    Lipid dosage forms provide an interesting potential for controlled drug delivery. In contrast to frequently used poly(ester) based devices for parenteral administration, they do not lead to acidification upon degradation and potential drug inactivation, especially in the case of protein drugs and other acid-labile active agents. The aim of this article is to give an overview on the current state of the art of mathematical modeling of drug release from this type of advanced drug delivery systems. Empirical and semi-empirical models are described as well as mechanistic theories, considering diffusional mass transport, potentially limited drug solubility and the leaching of other, water-soluble excipients into the surrounding bulk fluid. Various practical examples are given, including lipid microparticles, beads and implants, which can successfully be used to control the release of an incorporated drug during periods ranging from a few hours up to several years. The great benefit of mechanistic mathematical theories is the possibility to quantitatively predict the effects of different formulation parameters and device dimensions on the resulting drug release kinetics. Thus, in silico simulations can significantly speed up product optimization. This is particularly useful if long release periods (e.g., several months) are targeted, since experimental trial-and-error studies are highly time-consuming in these cases. In the future it would be highly desirable to combine mechanistic theories with the quantitative description of the drug fate in vivo, ideally including the pharmacodynamic efficacy of the treatments.

  9. Swelling and drug release from oral thin films (OTFs)

    NASA Astrophysics Data System (ADS)

    Adrover, A.; Casadei, M. A.; Paolicelli, P.; Petralito, S.; Varani, G.

    2016-05-01

    We investigate the characteristic time-scales for swelling and drug release from polymeric thin films for buccal delivery. In this work, novel OTFs were prepared combining Gellan gum, a natural polysaccharide well known in the pharmaceutical field, along with Glycerol, used as plasticizer. A new millifluidic flow-through device is adopted for in-vitro release tests.

  10. Drug release from pH-sensitive polymeric micelles with different drug distributions: insight from coarse-grained simulations.

    PubMed

    Nie, Shu Yu; Lin, Wen Jing; Yao, Na; Guo, Xin Dong; Zhang, Li Juan

    2014-10-22

    How to control the release of drugs from pH-sensitive polymeric micelles is an issue of common concern, which is important to the effectiveness of the micelles. The components and properties of polymers can notably influence the drug distributions inside micelles which is a key factor that affects the drug release from the micelles. In this work, the dissipative particle dynamics simulation method is first used to study the structural transformation of micelles during the protonation process and the drug release process from micelles with different drug distributions. And then the effects of polymer structures, including different lengths of hydrophilic blocks, pH-sensitive blocks and hydrophobic blocks, on drug release are also studied. In the end, several corresponding design principles of pH-sensitive polymers for drug delivery are proposed according to the simulation results. This work is in favor of establishing qualitative rules for the design and optimization of congener polymers for desired drug delivery, which is of great significance to provide a potential approach for the development of new multiblock pH-sensitive polymeric micelles.

  11. Poly(lactide-co-glycolide)-methoxy-poly(ethylene glycol) nanoparticles: drug loading and release properties.

    PubMed

    Katsikogianni, Georgia; Avgoustakis, Konstantinos

    2006-01-01

    In this work, the drug loading and in vitro release properties of PLGA-mPEG nanoparticles were studied. Three methyl-xanthine derivatives differing significantly in aqueous solubility, i.e., caffeine, theophylline, and theobromine, were employed as model drugs. Two different PLGA-mPEG copolymer compositions, namely PLGA(40)mPEG(5) and PLGA(136)mPEG(5), were included in the study. The nanoparticles were prepared by a double emulsion technique. The drug release properties of the nanoparticles in phosphate buffered saline (PBS) and in human plasma were determined. An increase of the drug proportion in the feed led to increased drug loading. The composition of the PLGA-mPEG copolymer (PLGA/mPEG molar ratio) did not appear to affect drug loading and encapsulation. Caffeine exhibited higher loading in the nanoparticles than theobromine and this exhibited a little higher loading than theophylline. Solid-state solubility of the drug in PLGA-mPEG did not affect drug loading. Drug loading and encapsulation in the PLGA-mPEG nanoparticles appeared to be governed by the partition coefficient of the drug between the organic phase and the external aqueous phase employed in nanoparticle preparation. Relatively low loading and encapsulation values were obtained, suggesting that the physical entrapment of drugs in PLGA-mPEG nanoparticles could only be an option in the development of formulations of potent drugs. Only the release of the least water-soluble theobromine was efficiently sustained by its entrapment in the nanoparticles, indicating that the physical entrapment of drugs provides the means for the development of controlled-release PLGA-mPEG nanoparticulate formulations only in the case of drugs with low aqueous solubility.

  12. Aptamer-based liposomes improve specific drug loading and release.

    PubMed

    Plourde, Kevin; Derbali, Rabeb Mouna; Desrosiers, Arnaud; Dubath, Céline; Vallée-Bélisle, Alexis; Leblond, Jeanne

    2017-04-10

    Aptamer technology has shown much promise in cancer therapeutics for its targeting abilities. However, its potential to improve drug loading and release from nanocarriers has not been thoroughly explored. In this study, we employed drug-binding aptamers to actively load drugs into liposomes. We designed a series of DNA aptamer sequences specific to doxorubicin, displaying multiple binding sites and various binding affinities. The binding ability of aptamers was preserved when incorporated into cationic liposomes, binding up to 15equivalents of doxorubicin per aptamer, therefore drawing the drug into liposomes. Optimization of the charge and drug/aptamer ratios resulted in ≥80% encapsulation efficiency of doxorubicin, ten times higher than classical passively-encapsulating liposomal formulations and similar to a pH-gradient active loading strategy. In addition, kinetic release profiles and cytotoxicity assay on HeLa cells demonstrated that the release and therapeutic efficacy of liposomal doxorubicin could be controlled by the aptamer's structure. Our results suggest that the aptamer exhibiting a specific intermediate affinity is the best suited to achieve high drug loading while maintaining efficient drug release and therapeutic activity. This strategy was successfully applied to tobramycin, a hydrophilic drug suffering from low encapsulation into liposomes, where its loading was improved six-fold using aptamers. Overall, we demonstrate that aptamers could act, in addition to their targeting properties, as multifunctional excipients for liposomal formulations.

  13. Photocatalytic Degradation of Cell Membrane Coatings for Controlled Drug Release.

    PubMed

    Rao, Lang; Meng, Qian-Fang; Huang, Qinqin; Liu, Pei; Bu, Lin-Lin; Kondamareddy, Kiran Kumar; Guo, Shi-Shang; Liu, Wei; Zhao, Xing-Zhong

    2016-06-01

    Biomimetic cell-membrane-camouflaged particles with desirable features have been widely used for various biomedical applications. However, there are few reports on employing these particles for cancer drug delivery due to the failure of the membrane coatings to be efficiently degraded in the tumor microenvironment which hampers the drug release. In this work, core-shell SiO2 @TiO2 nanoparticles with enhanced photocatalytic activity are used for controlled degradation of surface erythrocyte membrane coatings. The antitumor drug docetaxel is encapsulated into nanocarriers to demonstrate the controlled drug release under ultraviolet irradiation, and the drug-loaded nanoparticles are further used for enhanced cancer cell therapy. Here, a simple but practical method for degradation of cell membrane coatings is presented, and a good feasibility of using cell membrane-coated nanocarriers for controlled drug delivery is demonstrated.

  14. Drug release from hydroethanolic gels. Effect of drug's lipophilicity (logP), polymer-drug interactions and solvent lipophilicity.

    PubMed

    Sawant, Prashant D; Luu, Dewitt; Ye, Rose; Buchta, Richard

    2010-08-30

    We demonstrate drug release properties from hydroethanolic formulations as a function of the drug's lipophilicity (logP), solvent lipophilicity and drug-polymer interactions, for the first time. A hydrophilic polymer, hydroxypropyl cellulose (HPC), provides the non-Fickian slower release of the lipophilic drug, lidocaine (logP=2.6) and the burst (Fickian) release of hydrophilic drug, lidocaine hydrochloride (logPdrugs helps predict the drug release properties. Hydrophobic Eudragit polymers provided the burst release of lidocaine. However, the cationic hydrophobic polymer (Eudragit E100) retained more lidocaine (approximately 50%) topically than other hydrophobic polymers: Eudragit S100 (anionic) and Eudragit RLPO (cationic copolymer with quaternary ammonium group) ( approximately 25% lidocaine retention) which release lidocaine systematically. Thus, minute changes in functional groups of hydrophobic polymers help tune the lidocaine release topically or systemically. An interaction between HPC and lidocaine as determined by FTIR helps the non-Fickian slower lidocaine release from HPC formulations. However, no interactions between lidocaine and hydrophobic Eudragit polymers explain the Fickian burst release of lidocaine from their formulations. A lipophilic solvent, isostearyl alcohol which when replacing ethanol by 30%, slows the release rate and enhances the topical adsorption of lidocaine. Thus, solvent lipophilicity also modulates drug release properties.

  15. Dendrimeric micelles for controlled drug release and targeted delivery

    PubMed Central

    Ambade, Ashootosh V.; Savariar, Elamprakash N.; Thayumanavan, S.

    2008-01-01

    This review highlights the developments in dendrimer-based micelles for drug delivery. Dendrimers, the perfectly branched monodisperse macromolecules, have certain structural advantages that make them attractive candidates as drug carriers for controlled release or targeted delivery. As polymeric micelle-based approaches precede the work in dendrimers, these are also discussed briefly. The review concludes with a perspective on possible applications of biaryl-based dendrimeric micelles that exhibit environment-dependent conformations, in drug delivery. PMID:16053329

  16. Drug release from porous silicon for stable neural interface

    NASA Astrophysics Data System (ADS)

    Sun, Tao; Tsang, Wei Mong; Park, Woo-Tae

    2014-02-01

    70 μm-thick porous Si (PSi) layer with the pore size of 11.1 ± 7.6 nm was formed on an 8-in. Si wafer via an anodization process for the microfabrication of a microelectrode to record neural signals. To reduce host tissue responses to the microelectrode and achieve a stable neural interface, water-soluble dexamethesone (Dex) was loaded into the PSi via incubation with the drug solution overnight. After the drug loading process, the pore size of PSi reduced to 4.7 ± 2.6 nm on the basis of scanning electron microscopic (SEM) images, while its wettability was remarkably enhanced. Fluorescence images demonstrated that Dex was loaded into the porous structure of the PSi. Degradation rate of the PSi was investigated by incubation in distilled water for 21 days. Moreover, the drug release profile of the Dex-loaded PSi was a combination of an initial burst release and subsequent sustained release. To evaluate cellular responses to the drug release from the PSi, primary astrocytes were seeded on the surface of samples. After 2 days of culture, the Dex-loaded PSi could not only moderately prevent astrocyte adhesion in comparison with Si, but also more effectively suppress the activation of primary astrocytes than unloaded PSi due to the drug release. Therefore, it might be an effective method to reduce host tissue responses and stabilize the quality of the recorded neural signal by means of loading drugs into the PSi component of the microelectrode.

  17. Effect of intragranular porosity on compression behaviour of and drug release from reservoir pellets.

    PubMed

    Tunón, Asa; Gråsjö, Johan; Alderborn, Göran

    2003-08-01

    In this study, reservoir pellets were prepared and their compression behaviour as well as the importance of their porosity for compression-induced changes in drug release was investigated. Pellets of three different porosities, consisting of microcrystalline cellulose and salicylic acid, were prepared by extrusion-spheronisation and spray-coated with ethyl cellulose (ethanol solution). Lubricated reservoir pellets were compressed and retrieved by deaggregation of the tablets. The retrieved pellets were analysed regarding porosity, thickness, surface area, shape and drug release. It was found that the coating did not significantly affect their compression behaviour. Compaction of pellets of high original porosity considerably affected densification and degree of deformation, whereas the effect on drug release was minor. For low porosity pellets the influence of compaction on drug release was appreciable, but only slight regarding densification and degree of deformation. In conclusion, the porosity of pellets is a potential factor that the formulator can use to optimize drug release and one that can affect the robustness of a formulation during manufacture. Moreover, the coating may be able to adapt to the densification and deformation of the pellets.

  18. Diisocyanate mediated polyether modified gelatin drug carrier for controlled release

    PubMed Central

    Vijayakumar, Vediappan; Subramanian, Kaliappagounder

    2013-01-01

    Gelatin is an extensively studied biopolymer hydrogel drug carrier due to its biocompatibility, biodegradability and non-toxicity of its biodegraded products formed in vivo. But with the pristine gelatin it is difficult to achieve a controlled and desirable drug release characteristics due to its structural and thermal lability and high solubility in aqueous biofluids. Hence it is necessary to modify its solubility and structural stability in biofluids to achieve controlled release features with improved drug efficacy and broader carrier applications. In the present explorations an effort is made in this direction by cross linking gelatin to different extents using hitherto not studied isocyanate terminated poly(ether) as a macrocrosslinker prepared from poly(ethylene glycol) and isophorone diisocyanate in dimethyl sulfoxide. The crosslinked samples were analyzed for structure by Fourier transform-infrared spectroscopy, thermal behavior through thermogravimetric analysis and differential scanning calorimetry. The cross linked gelatins were biodegradable, insoluble and swellable in biofluids. They were evaluated as a carrier for in vitro drug delivery taking theophylline as a model drug used in asthma therapy. The crosslinking of gelatin decreased the drug release rate by 10–20% depending upon the extent of crosslinking. The modeled drug release characteristics revealed an anomalous transport mechanism. The release rates for ampicillin sodium, 5-fluorouracil and theophylline drugs in a typical crosslinked gelatin carrier were found to depend on the solubility and hydrophobicity of the drugs, and the pH of the fluid. The observed results indicated that this material can prove its mettle as a viable carrier matrix in drug delivery applications. PMID:24493973

  19. Release mechanism and parameter estimation in drug-eluting stent systems: analytical solutions of drug release and tissue transport.

    PubMed

    McGinty, Sean; McKee, Sean; McCormick, Christopher; Wheel, Marcus

    2015-06-01

    Drug-eluting stents have significantly improved the treatment of coronary artery disease. They offer reduced rates of restenosis compared with their bare-metal predecessors and are the current gold standard in percutaneous coronary interventions. Drug-eluting stents have been approved for use in humans since 2002 and yet, despite the intensive research activity over the past decade, the drug release mechanism(s) and the uptake into the arterial wall are still poorly understood. While stent manufacturers have focussed primarily on empirical methods, several mathematical models have appeared in the literature considering the release problem, the uptake problem and also the coupled problem. However, two significant challenges that remain are in understanding the drug release mechanism(s) and also the determination of the various parameters characterizing the system. These include drug diffusion coefficients and dissolution constants in the stent polymer coating as well as drug diffusion coefficients, binding/uptake rates and the magnitude of the transmural convection in the arterial wall. In this paper we attempt to address these problems. We provide analytical solutions which, when compared with appropriate experiments, may allow the various parameters of the system to be estimated via the inverse problem. The analytical solutions which we provide here for drug release in vitro may thus be used as a tool for providing insights into the mechanism(s) of release.

  20. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice.

    PubMed

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi; Tran, Van-Thanh; Duan, Wei; Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh

    2016-10-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH6.8 at 37±0.5°C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug.

  1. Controlled release for local delivery of drugs: barriers and models.

    PubMed

    Weiser, Jennifer R; Saltzman, W Mark

    2014-09-28

    Controlled release systems are an effective means for local drug delivery. In local drug delivery, the major goal is to supply therapeutic levels of a drug agent at a physical site in the body for a prolonged period. A second goal is to reduce systemic toxicities, by avoiding the delivery of agents to non-target tissues remote from the site. Understanding the dynamics of drug transport in the vicinity of a local drug delivery device is helpful in achieving both of these goals. Here, we provide an overview of controlled release systems for local delivery and we review mathematical models of drug transport in tissue, which describe the local penetration of drugs into tissue and illustrate the factors - such as diffusion, convection, and elimination - that control drug dispersion and its ultimate fate. This review highlights the important role of controlled release science in development of reliable methods for local delivery, as well as the barriers to accomplishing effective delivery in the brain, blood vessels, mucosal epithelia, and the skin.

  2. Sol-gel encapsulation for controlled drug release and biosensing

    NASA Astrophysics Data System (ADS)

    Fang, Jonathan

    The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

  3. Effect of geometry on drug release from 3D printed tablets.

    PubMed

    Goyanes, Alvaro; Robles Martinez, Pamela; Buanz, Asma; Basit, Abdul W; Gaisford, Simon

    2015-10-30

    The aim of this work was to explore the feasibility of combining hot melt extrusion (HME) with 3D printing (3DP) technology, with a view to producing different shaped tablets which would be otherwise difficult to produce using traditional methods. A filament extruder was used to obtain approx. 4% paracetamol loaded filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3DP. Five different tablet geometries were successfully 3D-printed-cube, pyramid, cylinder, sphere and torus. The printing process did not affect the stability of the drug. Drug release from the tablets was not dependent on the surface area but instead on surface area to volume ratio, indicating the influence that geometrical shape has on drug release. An erosion-mediated process controlled drug release. This work has demonstrated the potential of 3DP to manufacture tablet shapes of different geometries, many of which would be challenging to manufacture by powder compaction.

  4. Drug releasing nanoplatforms activated by alternating magnetic fields.

    PubMed

    Mertz, Damien; Sandre, Olivier; Bégin-Colin, Sylvie

    2017-02-24

    The use of an alternating magnetic field (AMF) to generate non-invasively and spatially a localized heating from a magnetic nano-mediator has become very popular these last years to develop magnetic hyperthermia (MH) as a promising therapeutic modality already used in the clinics. AMF has become highly attractive this last decade over others radiations, as AMF allows a deeper penetration in the body and a less harmful ionizing effect. In addition to pure MH which induces tumor cell death through local T elevation, this AMF-generated magneto-thermal effect can also be exploited as a relevant external stimulus to trigger a drug release from drug-loaded magnetic nanocarriers, temporally and spatially. This review article is focused especially on this concept of AMF induced drug release, possibly combined with MH. The design of such magnetically responsive drug delivery nanoplatforms requires two key and complementary components: a magnetic mediator which collects and turns the magnetic energy into local heat, and a thermoresponsive carrier ensuring thermo-induced drug release, as a consequence of magnetic stimulus. A wide panel of magnetic nanomaterials/chemistries and processes are currently developed to achieve such nanoplatforms. This review article presents a broad overview about the fundamental concepts of drug releasing nanoplatforms activated by AMF, their formulations, and their efficiency in vitro and in vivo. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editors: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.

  5. Continuous drug release by sea anemone Nematostella vectensis stinging microcapsules.

    PubMed

    Tal, Yossi; Ayalon, Ari; Sharaev, Agnesa; Kazir, Zoya; Brekhman, Vera; Lotan, Tamar

    2014-01-27

    Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery.

  6. Modeling drug release from functionalized magnetic nanoparticles actuated by non-heating low frequency magnetic field

    NASA Astrophysics Data System (ADS)

    Golovin, Y.; Golovin, D.; Klyachko, N.; Majouga, A.; Kabanov, A.

    2017-02-01

    Various plausible acceleration mechanisms of drug release from nanocarriers composed of a single-domain magnetic nanoparticle core with attached long macromolecule chains activated by low frequency non-heating alternating magnetic field (AMF) are discussed. The most important system characteristics affecting the AMF exposure impact are determined. Impact of several reasonable mechanisms is estimated analytically or obtained using numerical modeling. Some conditions providing manifold release acceleration as a result from exposure in AMF are found.

  7. Development of novel small molecules for imaging and drug release

    NASA Astrophysics Data System (ADS)

    Cao, Yanting

    Small organic molecules, including small molecule based fluorescent probes, small molecule based drugs or prodrugs, and smart multifunctional fluorescent drug delivery systems play important roles in biological research, drug discovery, and clinical practices. Despite the significant progress made in these fields, the development of novel and diverse small molecules is needed to meet various demands for research and clinical applications. My Ph.D study focuses on the development of novel functional molecules for recognition, imaging and drug release. In the first part, a turn-on fluorescent probe is developed for the detection of intracellular adenosine-5'-triphosphate (ATP) levels based on multiplexing recognitions. Considering the unique and complicated structure of ATP molecules, a fluorescent probe has been implemented with improved sensitivity and selectivity due to two synergistic binding recognitions by incorporating of 2, 2'-dipicolylamine (Dpa)-Zn(II) for targeting of phospho anions and phenylboronic acid group for cis-diol moiety. The novel probe is able to detect intracellular ATP levels in SH-SY5Y cells. Meanwhile, the advantages of multiplexing recognition design concept have been demonstrated using two control molecules. In the second part, a prodrug system is developed to deliver multiple drugs within one small molecule entity. The prodrug is designed by using 1-(2-nitrophenyl)ethyl (NPE) as phototrigger, and biphenol biquaternary ammonium as the prodrug. With controlled photo activation, both DNA cross-linking agents mechlorethamine and o-quinone methide are delivered and released at the preferred site, leading to efficient DNA cross-links formation and cell death. The prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, but displays potent activity towards cancer cells (HeLa cells) upon UV activation. The multiple drug release system may hold a great potential for practical application. In the

  8. New high throughput screening method for drug release measurements.

    PubMed

    Pelczarska, Aleksandra; Delie, Florence; Domańska, Urszula; Carrupt, Pierre-Alain; Martel, Sophie

    2013-09-01

    In the field of drug delivery systems, microparticles made of polymeric matrix appear as an attractive approach. The in vitro release kinetic profile is crucial information when developing new particulate formulations. These data are essential for batch to batch comparison, quality control as well as for anticipation of in vivo behavior to select the best formulation to go further in preclinical investigations. The methods available present common drawbacks such as the time- and compound-consumption that does not fit with formulation screening requirements in early development stages. In this study, a new microscale high throughput screening (HTS) method has been developed to investigate drug release kinetic from piroxicam-loaded polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA) microparticles. The method is a sample- and separation-based method where separation is performed by filtration using 96-well micro filter plates. 96 experiments can therefore be performed on one plate in one time in a fully automated way and with a very low sample and particle consumption. The influence of different parameters controlling release profiles was also investigated using this technique. The HTS method gave the same release profile than the standard dialysis method. Shaking, particle concentration, and the nature of the release medium were found to be of influence. The HTS method appears as a reliable method to evaluate drug release from particles with smaller standard deviation and less consumption of material.

  9. Current strategies for sustaining drug release from electrospun nanofibers

    PubMed Central

    Chou, Shih-Feng; Carson, Daniel; Woodrow, Kim A.

    2017-01-01

    Electrospun drug-eluting fibers are emerging as a novel dosage form for multipurpose prevention against sexually transmitted infections, including HIV, and unintended pregnancy. Previous work from our lab and others show the versatility of this platform to deliver large doses of physico-chemically diverse agents. However, there is still an unmet need to develop practical fiber formulations for water-soluble small molecule drugs needed at high dosing due to intrinsic low potency or desire for sustained prevention. To date, most sustained release fibers have been restricted to the delivery of biologics or hydrophobic small molecules at low drug loading of typically < 1 wt.%, which is often impractical for most clinical applications. For hydrophilic small molecule drugs, their high aqueous solubility and poor partitioning and incompatibility with insoluble polymers make long-term release even more challenging. Here we investigate several existing strategies to sustain release of hydrophilic small molecule drugs that are highly-loaded in electrospun fibers. In particular, we investigate what is known about the design constraints required to realize multi-day release from fibers fabricated from uniaxial and coaxial electrospinning. PMID:26363300

  10. Electrospun nanofibers-mediated on-demand drug release.

    PubMed

    Chen, Menglin; Li, Yan-Fang; Besenbacher, Flemming

    2014-11-01

    A living system has a complex and accurate regulation system with intelligent sensor-processor-effector components to enable the release of vital bioactive substances on demand at a specific site and time. Stimuli-responsive polymers mimic biological systems in a crude way where an external stimulus results in a change in conformation, solubility, or alternation of the hydrophilic/hydrophobic balance, and consequently release of a bioactive substance. Electrospinning is a straightforward and robust method to produce nanofibers with the potential to incorporate drugs in a simple, rapid, and reproducible process. This feature article emphasizes an emerging area using an electrospinning technique to generate biomimetic nanofibers as drug delivery devices that are responsive to different stimuli, such as temperature, pH, light, and electric/magnetic field for controlled release of therapeutic substances. Although at its infancy, the mimicry of these stimuli-responsive nanofibers to the function of the living systems includes both the fibrous structural feature and bio-regulation function as an on demand drug release depot. The electrospun nanofibers with extracellular matrix morphology intrinsically guide cellular drug uptake, which will be highly desired to translate the promise of drug delivery for the clinical success.

  11. Current strategies for sustaining drug release from electrospun nanofibers.

    PubMed

    Chou, Shih-Feng; Carson, Daniel; Woodrow, Kim A

    2015-12-28

    Electrospun drug-eluting fibers are emerging as a novel dosage form for multipurpose prevention against sexually transmitted infections, including HIV, and unintended pregnancy. Previous work from our lab and others show the versatility of this platform to deliver large doses of physico-chemically diverse agents. However, there is still an unmet need to develop practical fiber formulations for water-soluble small molecule drugs needed at high dosing due to intrinsic low potency or desire for sustained prevention. To date, most sustained release fibers have been restricted to the delivery of biologics or hydrophobic small molecules at low drug loading of typically <1 wt.%, which is often impractical for most clinical applications. For hydrophilic small molecule drugs, their high aqueous solubility and poor partitioning and incompatibility with insoluble polymers make long-term release even more challenging. Here we investigate several existing strategies to sustain release of hydrophilic small molecule drugs that are highly-loaded in electrospun fibers. In particular, we investigate what is known about the design constraints required to realize multi-day release from fibers fabricated from uniaxial and coaxial electrospinning.

  12. Effect of drug solubility and lipid carrier on drug release from lipid nanoparticles for dermal delivery.

    PubMed

    Zoubari, Gaith; Staufenbiel, Sven; Volz, Pierre; Alexiev, Ulrike; Bodmeier, Roland

    2017-01-01

    Lipid nanoparticles have gained increased interest in the field of dermal products because of various advantages such as improved drug absorption and controlled drug release. The main objective was to investigate the influence of drug solubility and type of lipid carrier on the in vitro drug release. Drugs of different solubilities in the release medium PBS pH 7.4 (dexamethasone: 0.1mg/ml and diclofenac sodium: 5.0mg/ml) and three different lipids (in which the drugs had the highest solubility), Gelucire® 50/13 (solid lipid, mp: 50°C), Witepsol® S55 (solid lipid, mp: 33.5-35.5°C) and Capryol® 90 (liquid lipid) were chosen. The lipid nanoparticles were prepared by high shear homogenization. All nanosuspensions were in the nanometer range (up to 400nm) and the drug encapsulation efficiency was between 84% and 95%. The drug release was prolonged over 48h without an initial burst release and was dependent on the lipid carrier. Formulations containing a higher amount of solid Gelucire® 50/13 released the drugs slower due to the high affinity of the drugs to this lipid product. Inclusion of the liquid lipid Capryol® 90 resulted in a less organized lipidic structures (softer particles) and therefore a faster drug release. Despite its higher water solubility, diclofenac was released slower than dexamethasone because of its higher solubility in the lipid carriers. DSC studies indicated a partial miscibility between the solid lipids and a good miscibility between the solid and liquid lipids. Primary studies using total internal reflection fluorescence (TIRF) microscopy indicated that it is possible to detect individual fluorescently labeled dexamethasone (DXM-F) molecules dissolved in the liquid lipid Capryol® 90. These studies will allow for the precise determination of the drug distribution within the lipid carrier, and the changes upon drug release. In conclusion, lipid carrier type and drug solubility in the lipid have a large influence on the in vitro drug

  13. [Drug release system controlled by near infrared light].

    PubMed

    Niidome, Takuro

    2013-01-01

    Gold nanorods have absorption bands in the near-infrared region; in this spectral range, light penetrates deeply into tissues. The absorbed light energy is converted into heat by gold nanorods. This is the so-called photothermal effect. Gold nanorods are therefore expected to act not only as thermal converters for photothermal therapy, but also as controllers for drug-release systems responding to irradiation with near-infrared light. To achieve a controlled-release system that could be triggered by light irradiation, the gold nanorods were modified with double-stranded DNA (dsDNA). When the dsDNA-modified gold nanorods were irradiated with near-infrared light, single-stranded DNA (ssDNA) was released from the gold nanorods because of the photothermal effect. The release of ssDNA was also observed in tumors grown on mice after near-infrared light irradiation. We also proposed a different controlled-release system responding to near-infrared light. Gold nanorods were modified with polyethylene glycol (PEG) through Diels-Alder cycloadducts. When the gold nanorods were irradiated with near-infrared light, the PEG chains were released from the gold nanorods because of the retro Diels-Alder reaction induced by the photothermal effect. Such controlled-release systems triggered by near-infrared light irradiation will be expanded for gold nanorod drug delivery system applications.

  14. Transdermal Delivery Devices: Fabrication, Mechanics and Drug Release from Silk**

    PubMed Central

    Raja, Waseem K.; MacCorkle, Scott; Diwan, Izzuddin M.; Abdurrob, Abdurrahman; Lu, Jessica; Omenetto, Fiorenzo G.; Kaplan, David L.

    2013-01-01

    Microneedles are a relatively simple, minimally invasive and painless approach to deliver drugs across the skin. However, there remain limitations with this approach because of the materials most commonly utilized for such systems. Silk protein, with tunable and biocompatibility properties, is a useful biomaterial to overcome the current limitations with microneedles. Silk devices preserve drug activity, offer superior mechanical properties and biocompatibility, can be tuned for biodegradability, and can be processed under aqueous, benign conditions. In the present work, we report the fabrication of dense microneedle arrays from silk with different drug release kinetics. The mechanical properties of the microneedle patches are tuned by post-fabrication treatments or by loading the needles with silk microparticles to increase capacity and mechanical strength. Drug release is further enhanced by the encapsulation of the drugs in the silk matrix and coating with a thin dissolvable drug layer. The microneedles are used on human cadaver skin and drugs were delivered successfully. The various attributes demonstrated suggest that silk-based microneedle devices can provide significant benefit as a platform material for transdermal drug delivery. PMID:23653252

  15. Organically modified titania nanoparticles for sustained drug release applications.

    PubMed

    Sethi, Komal; Roy, Indrajit

    2015-10-15

    In this paper, we report the synthesis, characterization of drug-doped organically modified titania nanoparticles, and their applications in sustained drug release. The drug-doped nanoparticles were synthesized in the hydrophobic core of oil-in-water microemulsion medium. Structural aspects obtained through TEM and FESEM depicted that organically modified titania nanoparticles are monodispersed with spherical morphology, with an average size of around 200 nm. Their polymorphic forms and porosity were determined using powder XRD and BET, respectively, which showed that they are present in the anatase form, with a surface area of 136.5 m(2)/g and pore-diameter of 5.23 nm. After synthesis and basic structural characterizations, optical properties were studied for both fluorophore and drug encapsulated nanoparticles. The results showed that though the optical properties of the fluorophore are partially diminished upon nanoencapsulation, it became more stable against chemical quenching. The nanoparticles showed pH-dependent drug release pattern. In vitro studies showed that the nanoparticles were efficiently uptaken by cells. Cell viability assay results showed that though the placebo nanoparticles are non-cytotoxic, the drug-doped nanoparticles show drug-induced toxicity. Therefore, such porous nanoparticles can be used in non-toxic drug delivery applications.

  16. Cellulose, chitosan, and keratin composite materials. Controlled drug release.

    PubMed

    Tran, Chieu D; Mututuvari, Tamutsiwa M

    2015-02-03

    A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm(+)Cl(-)]), an ionic liquid, was used as the sole solvent, and because the [BMIm(+)Cl(-)] used was recovered, the method is green and recyclable. Fourier transform infrared spectroscopy results confirm that KER, CS, and CEL remain chemically intact in the composites. Tensile strength results expectedly show that adding CEL or CS into KER substantially increases the mechanical strength of the composites. We found that CEL, CS, and KER can encapsulate drugs such as ciprofloxacin (CPX) and then release the drug either as a single or as two- or three-component composites. Interestingly, release rates of CPX by CEL and CS either as a single or as [CEL+CS] composite are faster and independent of concentration of CS and CEL. Conversely, the release rate by KER is much slower, and when incorporated into CEL, CS, or CEL+CS, it substantially slows the rate as well. Furthermore, the reducing rate was found to correlate with the concentration of KER in the composites. KER, a protein, is known to have secondary structure, whereas CEL and CS exist only in random form. This makes KER structurally denser than CEL and CS; hence, KER releases the drug slower than CEL and CS. The results clearly indicate that drug release can be controlled and adjusted at any rate by judiciously selecting the concentration of KER in the composites. Furthermore, the fact that the [CEL+CS+KER] composite has combined properties of its components, namely, superior mechanical strength (CEL), hemostasis and bactericide (CS), and controlled drug release (KER), indicates that this novel composite can be used in ways which hitherto were not possible, e.g., as a high-performance bandage to treat chronic and ulcerous wounds.

  17. Microbead design for sustained drug release using four natural gums.

    PubMed

    Odeku, Oluwatoyin A; Okunlola, Adenike; Lamprecht, Alf

    2013-07-01

    Four natural gums, namely albizia, cissus, irvingia and khaya gums have been characterized and evaluated as polymers for the formulation of microbeads for controlled delivery of diclofenac sodium. The natural gums were characterized for their material properties using standard methods. Diclofenac microbeads were prepared by ionotropic gelation using gel blends of the natural gums and sodium alginate at different ratios and zinc chloride solution (10%w/v) as the crosslinking agent. The microbeads were assessed using SEM, swelling characteristics, drug entrapment efficiencies and release properties. Data obtained from in vitro dissolution studies were fitted to various kinetic equations to determine the kinetics and mechanisms of drug release, and the similarity factor, f2, was used to compare the different formulations. The results showed that the natural gum polymers varied considerably in their material properties. Spherical and discrete microbeads with particle size of 1.48-2.41 μm were obtained with entrapment efficiencies of 44.0-71.3%w/w. Drug release was found to depend on the type and concentration of polymer gum used with formulations containing gum:alginate ratio of 3:1 showing the highest dissolution times. Controlled release of diclofenac was obtained over for 5h. Drug release from the beads containing the polymer blends of the four gums and sodium alginate fitted the Korsmeyer-Peppas model which appeared to be dependent on the nature of natural gum in the polymer blend while the beads containing alginate alone fitted the Hopfenberg model. Beads containing albizia and cissus had comparable release profiles to those containing khaya (f2>50). The results suggest that the natural gums could be potentially useful for the formulation controlled release microbeads.

  18. Understanding and managing the impact of HPMC variability on drug release from controlled release formulations.

    PubMed

    Zhou, Deliang; Law, Devalina; Reynolds, Judie; Davis, Lynn; Smith, Clifford; Torres, Jose L; Dave, Viraj; Gopinathan, Nishanth; Hernandez, Daniel T; Springman, Mary Kay; Zhou, Casey Chun

    2014-06-01

    The purpose of this study is to identify critical physicochemical properties of hydroxypxropyl methylcellulose (HPMC) that impact the dissolution of a controlled release tablet and develop a strategy to mitigate the HPMC lot-to-lot and vendor-to-vendor variability. A screening experiment was performed to evaluate the impacts of methoxy/hydroxypropyl substitutions, and viscosity on drug release. The chemical diversity of HPMC was explored by nuclear magnetic resonance (NMR), and the erosion rate of HPMC was investigated using various dissolution apparatuses. Statistical evaluation suggested that the hydroxypropyl content was the primary factor impacting the drug release. However, the statistical model prediction was not robust. NMR experiments suggested the existence of structural diversity of HPMC between lots and more significantly between vendors. Review of drug release from hydrophilic matrices indicated that erosion is a key aspect for both poorly soluble and soluble drugs. An erosion rate method was then developed, which enabled the establishment of a robust model and a meaningful HPMC specification. The study revealed that the overall substitution level is not the unique parameter that dictates its release-controlling properties. Fundamental principles of polymer chemistry and dissolution mechanisms are important in the development and manufacturing of hydrophilic matrices with consistent dissolution performance.

  19. Thermally Responsive Hydrogel Blends: A General Drug Carrier Model for Controlled Drug Release.

    PubMed

    Ma, Chongbo; Shi, Ye; Pena, Danilo A; Peng, Lele; Yu, Guihua

    2015-06-15

    Thermally responsive hydrogels have drawn significant research attention recently because of their simple use as drug carrier at human body temperature. Here we design a hybrid hydrogel that incorporates a hydrophilic polymer, polyethyleneimine (PEI), into the thermally responsive hydrogel poly(N-isopropylacrylamide) (PNIPAm), as a general drug carrier model for controlled drug release. In this work, on one hand, PEI modifies the structure and the size of the pores in the PNIPAm hydrogel. On the other hand, PEI plays an important role in tuning the water content in the hydrogel and controls the water release rate of the hydrogel below the lower critical solution temperature (LCST), resulting in a tunable release rate of the drugs at human body temperature (37 °C). Different release rates are shown as different amounts of PEI are incorporated. PEI controls the release rate, dependent on the charge characteristics of the drugs. The hydrogel blends described in this work extend the concept of a general drug carrier for loading both positively and negatively charged drugs, as well as the controlled release effect.

  20. Drug release from hydrazone-containing peptide amphiphiles

    SciTech Connect

    Matson, John B.; Stupp, Samuel I.

    2012-03-15

    Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for release of the drug nabumetone from nanofiber gels. On-resin addition of the novel compound tri-Boc-hydrazido adipic acid to a lysine E-amine allowed for precise placement of a hydrazide in a peptide sequence.

  1. Prediction of drug release from HPMC matrices: effect of physicochemical properties of drug and polymer concentration.

    PubMed

    Fu, X C; Wang, G P; Liang, W Q; Chow, M S S

    2004-03-05

    A working equation to predict drug release from hydroxypropyl methylcellulose (HPMC) matrices was derived using a training set of HPMC matrices having different HPMC concentration (w/w, 16.5-55%) and different drugs (solubilities of 1.126-125.5 g/100 ml in water and molecular volumes of 0.1569-0.4996 nm(3)). The equation was log(M(t)/M( infinity ))=-0.6747+1.027 log t -0.1759 (log C(s)) log t +0.4027 (log V) log t -1.041C(H) +0.3213 (log C(s)) C(H) -0.4101 (log V) C(H) -0.3521 (log V) log C(s) (n=263, r=0.9831), where M(t) is the amount of drug released at time t, M( infinity ) the amount of drug released over a very long time, which corresponds in principle to the initial loading, t the release time (h), C(s) the drug solubility in water (g/100 ml), V the volume of drug molecule (nm(3)), and C(H) is HPMC concentration (w/w). The benefit of the novel model is to predict M(t)/M( infinity ) values of a drug from formulation and its physicochemical properties, so applicable to the HPMC matrices of different polymer levels and different drugs including soluble drugs and slightly soluble drugs.

  2. Contamination and restoration of an estuary affected by phosphogypsum releases.

    PubMed

    Villa, M; Mosqueda, F; Hurtado, S; Mantero, J; Manjón, G; Periañez, R; Vaca, F; García-Tenorio, R

    2009-12-15

    The Huelva Estuary in Huelva, Spain, has been one of the most studied environmental compartments in the past years from the point of view of naturally occurring radioactive material (NORM) releases. It has been historically affected by waste releases, enriched in radionuclides from the U-decay series, from factories located in the area devoted to the production of phosphoric acid and phosphate fertilizers. Nevertheless, changes in national regulations forced a new waste management practice in 1998, prohibiting releases of phosphogypsum into the rivers. The input of natural radionuclides from phosphate factories to rivers was drastically reduced. Because of this there was a unique opportunity for the study of the response of a contaminated environmental compartment, specifically an estuary affected by tidal influences, after the cessation of the contaminant releases to, in this case, the Huelva Estuary (henceforth referred to as the Estuary). To investigate the environmental response to this new discharge regime, the specific activities of radionuclides 226Ra and 210Pb in water and sediment samples collected in four campaigns (from 1999 to 2005) were determined and compared with pre-1998 values. From this study it is possible to infer the most effective mechanisms of decontamination for the Estuary. Decontamination rates of 210Pb and 226Ra in the sediments and water have been calculated using exponential fittings and corresponding half-lives have been deduced from them. The cleaning half-life in the whole area of the Estuary is about 6 and 3.5 years for 226Ra and 210Pb respectively. The observed trend clearly shows that contamination of the Estuary by natural radionuclides is now decreasing and radioactive levels in waters and sediments are approaching the natural background references. This work attempts to evaluate whether it can be expected that the decontamination of the enhanced levels of natural radioactivity in the Estuary can be performed via natural

  3. Controlled Release System for Localized and Sustained Drug Delivery Applications

    NASA Astrophysics Data System (ADS)

    Rodriguez, Lidia Betsabe

    Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is

  4. Targeted drug delivery and enhanced intracellular release using functionalized liposomes

    NASA Astrophysics Data System (ADS)

    Garg, Ashish

    The ability to target cancer cells using an appropriate drug delivery system can significantly reduce the associated side effects from cancer therapies and can help in improving the overall quality of life, post cancer survival. Integrin alpha5beta1 is expressed on several types of cancer cells, including colon cancer and plays an important role in tumor growth and metastasis. Thus, the ability to target the integrin alpha 5beta1 using an appropriate drug delivery nano-vector can significantly help in inhibiting tumor growth and reducing tumor metastasis. The work in this thesis focuses on designing and optimizing, functionalized stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that specifically target the integrin alpha5beta1. The PEG provides a steric barrier allowing the liposomes to circulate in the blood for longer duration and the functionalizing moiety, PR_b peptide specifically recognizes and binds to integrin alpha5beta1 expressing cells. The work demonstrates that by optimizing the amount of PEG and PR_b on the liposomal interface, nano-vectors can be engineered that bind to CT26.WT colon cancer cells in a specific manner and internalize through alpha 5beta1-mediated endocytosis. To further improve the efficacy of the system, PR_b functionalized pH-sensitive stealth liposomes that exhibit triggered release under mild acidic conditions present in endocytotic vesicles were designed. The study showed that PR_b functionalized pH-sensitive stealth liposomes, undergo destabilization under mildly acidic conditions and incorporation of the PR_b peptide does not significantly affect the pH-sensitivity of the liposomes. PR_b functionalized pH-sensitive stealth liposomes bind to CT26.WT colon carcinoma cells that express integrin alpha5beta 1, undergo cellular internalization, and release their load intracellularly in a short period of time as compared to other formulations. PR_b-targeted pH-sensitive stealth liposomes encapsulating 5

  5. Graphene as a photothermal switch for controlled drug release

    NASA Astrophysics Data System (ADS)

    Matteini, Paolo; Tatini, Francesca; Cavigli, Lucia; Ottaviano, Stefania; Ghini, Giacomo; Pini, Roberto

    2014-06-01

    Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor-made pharmacological treatments of chronic diseases, including cancer, anaemia and diabetes.Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor

  6. Drug incorporation and release of water soluble drugs from novel functionalized poly(glycerol adipate) nanoparticles.

    PubMed

    Puri, Sanyogita; Kallinteri, Paraskevi; Higgins, Sean; Hutcheon, Gillian A; Garnett, Martin C

    2008-01-04

    We have previously demonstrated the ability of poly(glycerol adipate) backbone (PGA) and PGA polymer backbone substituted with varying amounts of pendant C(18) chain length acyl groups to yield Dexamethasone phosphate DXMP loaded nanoparticles. The aim of this study was to obtain a deeper understanding of the underlying principles responsible for good drug incorporation and controlled release of drugs from poly (glycerol adipate) (PGA) nanoparticles. We compared the incorporation of the water soluble drugs DXMP and Cytosine arabinoside (CYT-ARA) in both unmodified and substituted PGA polymers. We investigated the effect of change in acyl group chain length and the degree of substitution on the physicochemical properties, drug loading and release of DXMP and CYT-ARA. Nanoparticles were prepared by the interfacial deposition technique and the simultaneous emulsification method. Amongst the nanoparticles prepared using acylated polymers with varying chain lengths (C(2) to C(10)) for DXMP incorporation, polymers with acyl group chain lengths containing 8 carbon atoms (C(8)) showed maximum drug incorporation. Amongst the C(8) series, polymers with 100% acylation provided both good drug incorporation and a controlled release for DXMP while for CYT-ARA it was the unsubstituted polymer backbone that had maximum drug loading and slower release. A number of inter-related factors are responsible for producing particles with particular size, zeta potential, drug loading and release characteristics. Drug loading and release from nanoparticles are primarily influenced by the nature of interactions between the drug and polymers which in turn depend upon the type of drug used and the physical chemistry of the polymer.

  7. Drug release from liposome coated hydrogels for soft contact lenses: the blinking and temperature effect.

    PubMed

    Paradiso, P; Colaço, R; Mata, J L G; Krastev, R; Saramago, B; Serro, A P

    2016-05-18

    In this article, liposome-based coatings aiming to control drug release from therapeutic soft contact lenses (SCLs) materials are analyzed. A PHEMA based hydrogel material loaded with levofloxacin is used as model system for this research. The coatings are formed by polyelectrolyte layers containing liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DMPC + cholesterol (DMPC + CHOL). The effect of friction and temperature on the drug release is investigated. The aim of the friction tests is to simulate the blinking of the eyelid in order to verify if the SCLs materials coated with liposomes are able to keep their properties, in particular the drug release ability. It was observed that under the study conditions, friction did not affect significantly the drug release from the liposome coated PHEMA material. In contrast, increasing the temperature of release leads to an increase of the drug diffusion rate through the hydrogel. This phenomenon is recorded both in the control and in the coated samples. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

  8. Modified drug release using atmospheric pressure plasma deposited siloxane coatings

    NASA Astrophysics Data System (ADS)

    Dowling, D. P.; Maher, S.; Law, V. J.; Ardhaoui, M.; Stallard, C.; Keenan, A.

    2016-09-01

    This pilot study evaluates the potential of atmospheric plasma polymerised coatings to modify the rate of drug release from polymeric substrates. The antibiotic rifampicin was deposited in a prototype multi-layer drug delivery system, consisting of a nebulized layer of active drug between a base layer of TEOS deposited on a plastic substrate (polystyrene) and an overlying layer of plasma polymerised PDMS. The polymerised TEOS and PDMS layers were deposited using a helium atmospheric plasma jet system. Elution of rifampicin was measured using UV-VIS spectroscopy, in addition to a antimicrobial well diffusion assay with an established indicator organism. The multi-layered plasma deposited coatings significantly extended the duration of release of the rifampicin from 24 h for the uncoated polymer to 144 h for the coated polymer.

  9. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    NASA Astrophysics Data System (ADS)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

    2011-02-01

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  10. Hollow mesoporous silica as a high drug loading carrier for regulation insoluble drug release.

    PubMed

    Geng, Hongjian; Zhao, Yating; Liu, Jia; Cui, Yu; Wang, Ying; Zhao, Qinfu; Wang, Siling

    2016-08-20

    The purpose of this study was to develop a high drug loading hollow mesoporous silica nanoparticles (HMS) and apply for regulation insoluble drug release. HMS was synthesized using hard template phenolic resin nanoparticles with the aid of cetyltrimethyl ammonium bromide (CTAB), which was simple and inexpensive. To compare the difference between normal mesoporous silica (NMS) and hollow mesoporous silica in drug loading efficiency, drug release behavior and solid state, NMS was also prepared by soft template method. Transmission electron microscopy (TEM), specific surface area analysis, FT-IR and zeta potential were employed to characterize the morphology structure and physicochemical property of these carriers. The insoluble drugs, carvedilol and fenofibrate(Car and Fen), were chosen as the model drug to be loaded into HMS and NMS. We also chose methylene blue (MB) as a basic dye to estimate the adsorption ability of these carriers from macroscopic and microscopic view, and the drug-loaded carriers were systematically studied by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and UV-vis spectrophotometry. What' more, the in vivo process of HMS was also study by confocal microscopy and in vivo fluorescence imaging. In order to confirm the gastrointestinal safety of HMS, the pathological examination of stomach and intestine also be evaluated. HMS allowed a higher drug loading than NMS and exhibited a relative sustained release curve, while NMS was immediate-release. And the effect of preventing drugs crystallization was weaker than NMS. As for in vivo process, HMS was cleared relatively rapidly from the mouse gastrointestinal and barely uptake by intestinal epithelial cell in this study due to its large particle size. And the damage of HMS to gastrointestinal could be ignored. This study provided a simple method to obtain high drug loading and regulation insoluble drug release, expanded the application of inorganic carriers in drug delivery system

  11. Modeling Drug-Carrier Interaction in the Drug Release from Nanocarriers

    PubMed Central

    Zeng, Like; An, Lingling; Wu, Xiaoyi

    2011-01-01

    Numerous nanocarriers of various compositions and geometries have been developed for the delivery and release of therapeutic and imaging agents. Due to the high specific surface areas of nanocarriers, different mechanisms such as ion pairing and hydrophobic interaction need to be explored for achieving sustained release. Recently, we developed a three-parameter model that considers reversible drug-carrier interaction and first-order drug release from liposomes. A closed-form analytical solution was obtained. Here, we further explore the ability of the model to capture the release of bioactive molecules such as drugs and growth factors from various nanocarriers. A parameter study demonstrates that the model is capable of resembling major categories of drug release kinetics. We further fit the model to 60 sets of experimental data from various drug release systems, including nanoparticles, hollow particles, fibers, and hollow fibers. Additionally, bootstrapping is used to evaluate the accuracy of parameter determination and validate the model in selected cases. The simplicity and universality of the model and the clear physical meanings of each model parameter render the model useful for the design and development of new drug delivery systems. PMID:21845225

  12. Drug release from calcium sulfate-based composites.

    PubMed

    Orellana, Bryan R; Hilt, J Zach; Puleo, David A

    2015-01-01

    To help reduce the need for autografts, calcium sulfate (CS)-based bone graft substitutes are being developed to provide a stable platform to aid augmentation while having the ability to release a broad range of bioactive agents. CS has an excellent reputation as a biocompatible and osteoconductive substance, but addition of bioactive agents may further enhance these properties. Samples were produced with either directly loaded small, hydrophobic molecule (i.e., simvastatin), directly loaded hydrophilic protein (i.e., lysozyme), or 1 and 10 wt % of fast-degrading poly(β-amino ester) (PBAE) particles containing protein. Although sustained release of directly loaded simvastatin was achieved, direct loading of small amounts of lysozyme resulted in highly variable release. Direct loading of a larger amount of protein generated a large burst, 65% of total loading, followed by sustained release of protein. Release of lysozyme from 1 wt % of PBAE particles embedded into CS was more controllable than when directly loaded, and for 10 wt % of protein-loaded PBAE particles, a higher burst was followed by sustained release, comparable to the results for the high direct loading. Compression testing determined that incorporation of directly loaded drug or drug-loaded PBAE particles weakened CS. In particular, PBAE particles had a significant effect on the strength of the composites, with a 25 and 80% decrease in strength for 1 and 10 wt % particle loadings, respectively. CS-based composites demonstrated the ability to sustainably release both macromolecules and small molecules, supporting the potential for these materials to release a range of therapeutic agents.

  13. Drug Release from Calcium Sulfate-Based Composites

    PubMed Central

    Orellana, Bryan R.; Hilt, J. Zach; Puleo, David A.

    2015-01-01

    To help reduce the need for autografts, calcium sulfate-based bone graft substitutes are being developed to provide a stable platform to aid augmentation while having the ability to release a broad range of bioactive agents. Calcium sulfate (CS) has an excellent reputation as a biocompatible and osteoconductive substance, but addition of bioactive agents may further enhance these properties. Samples were produced with either directly loaded small, hydrophobic molecule (i.e., simvastatin), directly loaded hydrophilic protein (i.e., lysozyme), or 1 and 10 wt% of H6 poly(β-amino ester) (PBAE) particles containing protein. Whereas sustained release of directly loaded simvastatin was achieved, direct loading of small amounts of lysozyme resulted in highly variable release. Direct loading of a larger amount of protein generated a large burst, 65% of total loading, followed by sustained release of protein. Release of lysozyme from 1 wt% PBAE particles embedded into CS was more controllable than when directly loaded, and for 10 wt% of protein-loaded PBAE particles, a higher burst was followed by sustained release, comparable to the results for the high direct loading. Compression testing determined that incorporation of directly loaded drug or drug-loaded PBAE particles weakened CS. In particular, PBAE particles had a significant effect on the strength of the composites, with a 25% and 80% decrease in strength for 1 wt% and 10 wt% particle loadings, respectively. CS-based composites demonstrated the ability to sustainably release both macromolecules and small molecules, supporting the potential for these materials to release a range of therapeutic agents. PMID:24788686

  14. Study of dissolution hydrodynamic conditions versus drug release from hypromellose matrices: the influence of agitation sequence.

    PubMed

    Asare-Addo, Kofi; Levina, Marina; Rajabi-Siahboomi, Ali R; Nokhodchi, Ali

    2010-12-01

    In this article, the influence of agitation in descending and ascending sequences as a systematic method development process for potentially discriminating fed and fasted states and evaluation of its effects on the drug release from swelling gel-forming hydrophilic matrix tablets were investigated. Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC)) were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus at 5, 10, 15, 20, 25 and 30 dips per minute (dpm). Agitation had a profound effect on the drug release from the HPMC K100LV matrices. Drug release in pH 1.2 changed from about 40% at 5 dpm to about 80% at 30 dpm over a 60 min period alone. The matrices containing HPMC K4M, K15M and K100M however were not significantly affected by the agitation rate. The similarity factor f2 was calculated using drug release at 10 dpm as a reference. The ascending agitations of 5-30 dpm and the descending order of agitation 30-5 dpm were also evaluated. Anomalous transport was the only kinetic of release for the K4M, K15M and K100M tablet matrices. The lower viscous polymer of K100LV had some matrices exhibiting Fickian diffusion as its kinetics of release. The use of systematic change of agitation method may indicate potential fed and fasted effects on drug release from hydrophilic matrices.

  15. Designer nanoparticles: Incorporating size, shape, and triggered release into nanoscale drug carriers

    PubMed Central

    Caldorera-Moore, Mary; Guimard, Nathalie; Shi, Li; Roy, Krishnendu

    2009-01-01

    Importance of the field Although significant progress has been made in delivering therapeutic agents through micro and nanocarriers, precise control over in vivo biodistribution and disease-responsive drug release has been difficult to achieve. This is critical for the success of next generation drug delivery devices, since newer drugs, designed to interfere with cellular functions, must be efficiently and specifically delivered to diseased cells. The major constraint in achieving this has been our limited repertoire of particle synthesis methods, especially at the nanoscale. Recent developments in generating shape-specific nanocarriers and the potential to combine stimuli-responsive release with nanoscale delivery devices show great promise in overcoming these limitations. Areas covered in this review Here we discuss how recent advancements in fabrication technology allow synthesis of highly monodisperse, stimuli-responsive, drug-carrying nanoparticles of precise geometries. We also review how particle properties, specifically shape and stimuli responsiveness, affect biodistribution, cellular uptake, and drug release. What the reader will gain The reader is introduced to recent developments in intelligent drug nanocarriers and new nanofabrication approaches that can be combined with disease-responsive biomaterials. This will provide insight into the importance of controlling particle geometry and incorporating stimuli responsive materials into drug delivery. PMID:20331355

  16. Electrically actuatable smart nanoporous membrane for pulsatile drug release.

    PubMed

    Jeon, Gumhye; Yang, Seung Yun; Byun, Jinseok; Kim, Jin Kon

    2011-03-09

    We report on the fabrication of electrically responsive nanoporous membrane based on polypyrrole doped with dodecylbenzenesulfonate anion (PPy/DBS) that was electropolymerized on the upper part of anodized aluminum oxide membrane. The membrane has regular pore size and very high pore density. Utilizing a large volume change of PPy/DBS depending on electrochemical state, the pore size was acutated electrically. The actuation of the pores was experimentally confirmed by in situ atomic force microscopy and in situ flux measurement. We also demonstrated successfully pulsatile (or on-demand) drug release by using fluorescently labeled protein as a model drug. Because of a fast switching time (less than 10 s) and high flux of the drugs, this membrane could be used for emergency therapy of angina pectoris and migraine, which requires acute and on-demand drug delivery, and hormone-related disease and metabolic syndrome.

  17. Mathematical modelling of the release of drug from porous, nonswelling transdermal drug-delivery devices.

    PubMed

    Lee, A J; King, J R; Hibberd, S

    1998-06-01

    A general model is presented for the release of drug from porous nonswelling, transdermal drug-delivery devices and it is shown to reduce to previously proposed models in suitable limits. The processes which govern the release of drug are considered to be diffusion of dissolved drug and dissolution of dispersed drug, both in the body of the device and in the device pores, and transfer of drug between the two domains. In the classical limit of large dissolution rates, the problem reduces to one of the moving-boundary type, and solution of this problem in the case where the initial drug loading is much greater than the drug solubility in the device yields expressions for the flux of drug to a perfect sink (modelling in vitro conditions). It is shown that behaviour greatly differing from the classical first-order drug delivery (alpha t 1/2) may be exhibited, depending upon the parameter regime. In some situations the dissolution rates may not be so large and solutions of the general model are derived in the case where the dispersed drug is considered to be undepleted and the diffusivity in the solvent-filled pores is much larger than in the body of the delivery device. Numerical studies are undertaken, and the coupling of delivery device and skin-diffusion models (in order to model the complete transdermal drug-delivery process) is also considered.

  18. Preparation of acetylsalicylic acid-acylated chitosan as a novel polymeric drug for drug controlled release.

    PubMed

    Liu, Changkun; Wu, Yiguang; Zhao, Liyan; Huang, Xinzheng

    2015-01-01

    The acetylsalicylic acid-acylated chitosan (ASACTS) with high degree of substitution (DS) was successfully synthesized, and characterized with FTIR, (1)H NMR and elemental analysis methods. The optimum synthesis conditions were obtained which gave the highest DS (about 60%) for ASACTS. Its drug release experiments were carried out in simulated gastric and intestine fluids. The results show that the drugs in the form of acetylsalicylic acid (ASA) and salicylic acid (SA) were released in a controlled manner from ASACTS only in simulated gastric fluid. The release profile can be best fitted with logistic and Weibull model. The research results reveal that ASACTS can be a potential polymeric drug for the controlled release of ASA and SA in the targeted gastric environment.

  19. A microfluidic chip for controlled release of drugs from microcapsules

    PubMed Central

    Cheng, Wen-Chuan; He, Yuan; Chang, An-Yi; Que, Long

    2013-01-01

    A new microfluidic device with liquid-droplet merging and droplet storage functions for the controlled release of drugs from microcapsules is reported. A switching channel is designed and integrated within the microfluidic device, facilitating the generation and capturing of uniform droplets by the storage chambers. The drug model is the MnCO3 microparticle, which is encapsulated by a microcapsule and fabricated using a simple layer-by-layer nanoassembly process. The merging function is used for dynamically adding the control solution into the droplets, which contain drugs within the microcapsules (DWμCs) and water. The storage chambers are used for collecting DWμCs-laden droplets so that the controlled-drug release in specific droplets can be monitored for an extended period of time, which has been experimentally implemented successfully. This technology could offer a promising technical platform for the long-term observation and studies of drug effects on specific cells in a controlled manner, which is especially useful for single cell analysis. PMID:24396536

  20. Effects of formulation and process variables on the release of a weakly basic drug from single unit extended release formulations.

    PubMed

    Kranz, H; Wagner, T

    2006-01-01

    A new commercially available extended release matrix material, Kollidon SR, composed of polyvinylacetate (PVA) and polyvinylpyrrolidone (PVP), was evaluated with respect to its ability to modulate the in vitro release of the weakly basic drug ZK 811 752. The effect of different formulation and process parameters on the release kinetics of ZK 811 752 from PVA/PVP based matrix tablets was investigated as a function of the (i) nature of excipient added to the drug-polymer mixtures, (ii) method of manufacturing (direct compression versus wet granulation), and (iii) effect of a post-compression curing step. ZK 811 752 containing extended release matrix tablets were successfully prepared by using Kollidon SR. The drug release from the matrix tablets increased by the addition of excipients such as maize starch, lactose and calcium phosphate. Addition of the highly swellable maize starch and the water-soluble lactose accelerated the drug release in a more pronounced manner compared to the water-insoluble calcium phosphate. Compound release from matrix tablets prepared by wet granulation was faster compared to the drug release from tablets prepared by direct compression. Post compression curing did not influence the drug release rate from drug-lactose-Kollidon SR formulations. Stability studies demonstrated no degradation of the drug substance and reproducible drug release patterns for matrix tablets stored at 25 degrees C/60% RH and 30 degrees C/70% RH for up to 6 months.

  1. Interfacial Fast Release Layer in Monodisperse Poly (lactic-co-glycolic acid) Microspheres Accelerates the Drug Release.

    PubMed

    Wu, Jun; Zhao, Xiaoli; Yeung, Kelvin W K; To, Michael K T

    2016-01-01

    Understanding microstructural evolutions of drug delivery devices during drug release process is essential for revealing the drug release mechanisms and controlling the drug release profiles. In this study, monodisperse poly (lactic-co-glycolic acid) microspheres in different diameters were fabricated by microfluidics in order to find out the relationships between the microstructural evolutions and the drug release profiles. It was found that poly (lactic-co-glycolic acid) microspheres underwent significant size expansion which took place from the periphery to the center, resulting in the formation of interfacial fast release layers. At the same time, inner pores were created and the diffusion rate was increased so that the early stage drug release was accelerated. Due to the different expansion rates, small poly (lactic-co-glycolic acid) microspheres tendered to follow homogeneous drug release while large poly (lactic-co-glycolic acid) microspheres tendered to follow heterogeneous drug release. This study suggests that the size expansion and the occurrence of interfacial fast release layer were important mechanisms for early stage drug release of poly (lactic-co-glycolic acid) microspheres.

  2. Controlled drug release on amine functionalized spherical MCM-41

    NASA Astrophysics Data System (ADS)

    Szegedi, Agnes; Popova, Margarita; Goshev, Ivan; Klébert, Szilvia; Mihály, Judit

    2012-10-01

    MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N2 physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin method and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41.

  3. Antipsychotic drugs inhibit prolactin release from rat anterior pituitary cells in culture by a mechanism not involving the dopamine receptor.

    PubMed

    West, B; Dannies, P S

    1979-04-01

    Bromocriptine, a dopamine agonist, inhibited secretion of PRL and did not affect GH release from rat anterior pituitary cells in culture. The reversal of this inhibition of PRL release by butaclamol, a dopamine antagonist, was stereospecific; 10 nM d-butaclamol completely reversed the inhibition caused by 10 nM bromocriptine, while l-butaclamol had no effect at concentrations up to 10 microM. However, both enantiomers at 10 microM inhibited PRL release to 30% and GH release to 91% of control values. Two other dopamine antagonists also inhibited hormone release. Haloperidol (10 microM) inhibited PRL release to 23% of control values and did not affect GH release; 3.3 microM pimozide inhibited PRL and GH release to 18% and 38% of control values, respectively. These data indicate that, the inhibition of PRL by antipsychotic drugs is not mediated through the dopamine receptor.

  4. Development of controlled drug release systems based on thiolated polymers.

    PubMed

    Bernkop-Schnürch, A; Scholler, S; Biebel, R G

    2000-05-03

    The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.

  5. Stress, glucocorticoids and glutamate release: effects of antidepressant drugs.

    PubMed

    Musazzi, Laura; Racagni, Giorgio; Popoli, Maurizio

    2011-08-01

    Stressful life events impact on memory, cognition and emotional responses, and are known to precipitate mood/anxiety disorders. It is increasingly recognized that stress and its neurochemical and endocrine mediators induce changes in glutamate synapses and circuitry, and this in turn modify mental states. Half a century after the monoamine hypothesis, it is widely accepted that maladaptive changes in excitatory/inhibitory circuitry have a primary role in the pathophysiology of mood/anxiety disorders. The neuroplasticity hypothesis posits that volumetric changes consistently found in limbic and cortical areas of depressed subjects are in good part due to remodeling of neuronal dendritic arbors and loss of synaptic spines. A considerable body of work, carried out with in vivo microdialysis as well as alternative methodologies, has shown that both stress and corticosterone treatment induce enhancement of activity-dependent glutamate release. Accordingly, results from preclinical studies suggest that stress- and glucocorticoid-induced enhancement of glutamate release and transmission plays a main role in the induction of maladaptive cellular effects, in turn responsible for dendritic remodeling. Additional recent work has showed that drugs employed for therapy of mood/anxiety disorders (antidepressants) prevent the enhancement of glutamate release induced by stress. Understanding the action of traditional drugs on glutamate transmission could be of great help in developing drugs that may work directly at this level.

  6. Drug release from pH-responsive thermogelling pentablock copolymers.

    PubMed

    Determan, Michael D; Cox, James P; Mallapragada, Surya K

    2007-05-01

    A novel pH-dependent injectable sustained delivery system was developed by utilizing a cationic pentablock copolymer that exhibits a thermoreversible sol-gel transition. Aqueous solutions of the pentablock copolymer, consisting of poly(2-diethylaminoethyl-methyl methacrylate)-poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)-poly(2-diethylaminoethyl-methyl methacrylate) (PDEAEM(25)-PEO(100)-PPO(65)-PEO(100)-PDEAEM(25)) exhibit temperature and pH dependent micellization due to the lower critical solution temperature of the PPO blocks and the polyelectrolyte character of the PDEAEM blocks, respectively. Aqueous solutions of the copolymers above 12 wt % are free flowing liquids at room temperature and form elastic physical hydrogels reversibly above 37 degrees C. Hydrophobic probe absorbance studies indicate that pentablock copolymer micelles increase the solubility of sparingly soluble drugs. Solutions of the pentablock copolymer that form gels at body temperature exhibit sustained zero-order release in in vitro experiments. The release rates of model drugs and proteins were significantly influenced by the pH of the release media, thereby making these polymers ideal candidates for modulated drug delivery.

  7. pH-controlled drug release for dental applications

    NASA Astrophysics Data System (ADS)

    Wironen, John Francis

    A large proportion of the dental fillings replaced at present are revised because of the perceived presence of a recurrent caries under or adjacent to the restoration. Many of these perceived caries may not exist, while others may go undetected. This work describes the preparation of drug loaded polymer microspheres that sense the presence of the bacteria that cause caries by the associated presence of acid by-products of digestion. These microspheres are designed to swell and release their antimicrobial drugs once the pH drops to a level that would normally cause caries. The preparation of the microspheres as well as their loading with potassium fluoride, chlorhexidine digluconate, chlorhexidine dihydrochloride, chlorhexidine diacetate, and tetracycline hydrochloride are described. A detailed study of the controlled release behavior of fluoride as a function of polymer composition and pH is presented first. A study of the release kinetics of potassium fluoride, chlorhexidine digluconate, diacetate, dihydrochloride, and tetracycline hydrochloride as a function of pH in the same polymer system is then presented. Additional studies of the swelling kinetics of chlorhexidine-loaded microspheres in various pH buffers are discussed with special reference to correlations with the controlled-release data. Finally, an experiment in which the microspheres are tested in an in vitro bacteria model that includes Streptococcus mutans is presented and discussed in detail.

  8. Zinc cross-linked hydroxamated alginates for pulsed drug release

    PubMed Central

    Raut, Neha S; Deshmukh, Prasad R; Umekar, Milind J; Kotagale, Nandkishor R

    2013-01-01

    Introduction: Alginates can be tailored chemically to improve solubility, physicochemical, and biological properties and its complexation with metal ion is useful for controlling the drug release. Materials And Methods: Synthesized N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were subsequently complexed with zinc to form beads. Hydroxamation of sodium alginate was confirmed by Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: The synthesized polymeric material exhibited reduced aqueous, HCl and NaOH solubility. The hydroxamated derivatives demonstrated pulsed release where change in pH of the dissolution medium stimulated the atenolol release. Conclusion: Atenolol loaded Zn cross-linked polymeric beads demonstrated the sustained the plasma drug levels with increased half-life. Although the synthesized derivatives greatly altered the aqueous solubility of sodium alginate, no significant differences in in vitro and in vivo atenolol release behavior amongst the N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were observed. PMID:24350039

  9. Abuse of Prescription (Rx) Drugs Affects Young Adults Most

    MedlinePlus

    ... Affects Young Adults Most Abuse of Prescription (Rx) Drugs Affects Young Adults Most Email Facebook Twitter Text Description of Infographic Young adults (age 18 to 25) are the biggest abusers of prescription (Rx) opioid pain relievers, ADHD stimulants, ...

  10. Tailored sequential drug release from bilayered calcium sulfate composites.

    PubMed

    Orellana, Bryan R; Puleo, David A

    2014-10-01

    The current standard for treating infected bony defects, such as those caused by periodontal disease, requires multiple time-consuming steps and often multiple procedures to fight the infection and recover lost tissue. Releasing an antibiotic followed by an osteogenic agent from a synthetic bone graft substitute could allow for a streamlined treatment, reducing the need for multiple surgeries and thereby shortening recovery time. Tailorable bilayered calcium sulfate (CS) bone graft substitutes were developed with the ability to sequentially release multiple therapeutic agents. Bilayered composite samples having a shell and core geometry were fabricated with varying amounts (1 or 10 wt.%) of metronidazole-loaded poly(lactic-co-glycolic acid) (PLGA) particles embedded in the shell and simvastatin directly loaded into either the shell, core, or both. Microcomputed tomography showed the overall layered geometry as well as the uniform distribution of PLGA within the shells. Dissolution studies demonstrated that the amount of PLGA particles (i.e., 1 vs. 10 wt.%) had a small but significant effect on the erosion rate (3% vs. 3.4%/d). Mechanical testing determined that introducing a layered geometry had a significant effect on the compressive strength, with an average reduction of 35%, but properties were comparable to those of mandibular trabecular bone. Sustained release of simvastatin directly loaded into CS demonstrated that changing the shell to core volume ratio dictates the duration of drug release from each layer. When loaded together in the shell or in separate layers, sequential release of metronidazole and simvastatin was achieved. By introducing a tunable, layered geometry capable of releasing multiple drugs, CS-based bone graft substitutes could be tailored in order to help streamline the multiple steps needed to regenerate tissue in infected defects.

  11. Tailored Sequential Drug Release from Bilayered Calcium Sulfate Composites

    PubMed Central

    Orellana, Bryan R.; Puleo, David A.

    2014-01-01

    The current standard for treating infected bony defects, such as those caused by periodontal disease, requires multiple time-consuming steps and often multiple procedures to fight the infection and recover lost tissue. Releasing an antibiotic followed by an osteogenic agent from a synthetic bone graft substitute could allow for a streamlined treatment, reducing the need for multiple surgeries and thereby shortening recovery time. Tailorable bilayered calcium sulfate (CS) bone graft substitutes were developed with the ability to sequentially release multiple therapeutic agents. Bilayered composite samples having a shell and core geometry were fabricated with varying amounts (1 or 10 wt%) of metronidazole-loaded poly poly(lactic-co-glycolic acid) (PLGA) particles embedded in the shell and simvastatin directly loaded into either the shell, core, or both. Microcomputed tomography (MicroCT) images showed the overall layered geometry as well as homogenous distribution of PLGA within the shells. Dissolution studies demonstrated that the amount of PLGA particles (i.e., 1 vs. 10 wt%) had a small but significant effect on the erosion rate (3% vs. 3.4% per day). Mechanical testing determined that introducing a layered geometry had a significant effect on the compressive strength, with an average reduction of 35%, but properties were comparable to mandibular trabecular bone. Sustained release of simvastatin directly loaded into CS demonstrated that changing the shell to core volume ratio dictates the duration of drug release from each layer. When loaded together in the shell or in separate layers, sequential release of metronidazole and simvastatin was achieved. By introducing a tunable layered geometry capable of releasing multiple drugs, CS-based bone graft substitutes could be tailored in order to help streamline multiple steps needed to regenerate tissue in infected defects. PMID:25175211

  12. Endocrine disrupting chemicals affect the gonadotropin releasing hormone neuronal network.

    PubMed

    Mueller, Johanna K; Heger, Sabine

    2014-04-01

    Endocrine disrupting chemicals have been shown to alter the pubertal process. The controlling levels of the Gonadotropin releasing hormone (GnRH) network involve GnRH itself, KiSS1, and the transcriptional regulators enhanced at puberty 1 (EAP1), Thyroid Transcription Factor 1 (TTF1), and Yin Yang 1 (YY1). While Genistein and Bisphenol A (BPA) have been shown to advance the advent of puberty, exposure to Dioxin delayed pubertal onset. Utilizing in vitro approaches, we observed that Genistein and BPA suppress inhibitory and activate stimulatory components of the GnRH network, while Dioxin exhibit an inhibitory effect at all regulatory hierarchical levels of the GnRH network. It repressed KiSS1, Gnrh, Ttf1 and Yy1 transcription via the xenobiotic response element (XRE), while EAP1 was not affected. Therefore, EDCs alter the neuroendocrine GnRH regulatory network at all hierarchical levels.

  13. pH-triggered drug release from biodegradable microwells for oral drug delivery.

    PubMed

    Nielsen, Line Hagner; Nagstrup, Johan; Gordon, Sarah; Keller, Stephan Sylvest; Østergaard, Jesper; Rades, Thomas; Müllertz, Anette; Boisen, Anja

    2015-01-01

    Microwells fabricated from poly-L-lactic acid (PLLA) were evaluated for their application as an oral drug delivery system using the amorphous sodium salt of furosemide (ASSF) as a model drug. Hot embossing of PLLA resulted in fabrication of microwells with an inner diameter of 240 μm and a height of 100 μm. The microwells were filled with ASSF using a modified screen printing technique, followed by coating of the microwell cavities with a gastro-resistant lid of Eudragit® L100. The release behavior of ASSF from the coated microwells was investigated using a μ-Diss profiler and a UV imaging system, and under conditions simulating the changing environment of the gastrointestinal tract. Biorelevant gastric medium (pH 1.6) was employed, after which a change to biorelevant intestinal release medium (pH 6.5) was carried out. Both μ-Diss profiler and UV imaging release experiments showed that sealing of microwell cavities with an Eudragit® layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug delivery system.

  14. Nanoporous anodic titanium dioxide layers as potential drug delivery systems: Drug release kinetics and mechanism.

    PubMed

    Jarosz, Magdalena; Pawlik, Anna; Szuwarzyński, Michał; Jaskuła, Marian; Sulka, Grzegorz D

    2016-07-01

    Nanoporous anodic titanium dioxide (ATO) layers on Ti foil were prepared via a three step anodization process in an electrolyte based on an ethylene glycol solution with fluoride ions. Some of the ATO samples were heat-treated in order to achieve two different crystallographic structures - anatase (400°C) and a mixture of anatase and rutile (600°C). The structural and morphological characterizations of ATO layers were performed using a field emission scanning electron microscope (SEM). The hydrophilicity of ATO layers was determined with contact angle measurements using distilled water. Ibuprofen and gentamicin were loaded effectively inside the ATO nanopores. Afterwards, an in vitro drug release was conducted for 24h under a static and dynamic flow conditions in a phosphate buffer solution at 37°C. The drug concentrations were determined using UV-Vis spectrophotometry. The absorbance of ibuprofen was measured directly at 222nm, whether gentamicin was determined as a complex with silver nanoparticles (Ag NPs) at 394nm. Both compounds exhibited long term release profiles, despite the ATO structure. A new release model, based on the desorption of the drug from the ATO top surface followed by the desorption and diffusion of the drug from the nanopores, was derived. The proposed release model was fitted to the experimental drug release profiles, and kinetic parameters were calculated.

  15. Encapsulation of methotrexate loaded magnetic microcapsules for magnetic drug targeting and controlled drug release

    NASA Astrophysics Data System (ADS)

    Chakkarapani, Prabu; Subbiah, Latha; Palanisamy, Selvamani; Bibiana, Arputha; Ahrentorp, Fredrik; Jonasson, Christian; Johansson, Christer

    2015-04-01

    We report on the development and evaluation of methotrexate magnetic microcapsules (MMC) for targeted rheumatoid arthritis therapy. Methotrexate was loaded into CaCO3-PSS (poly (sodium 4-styrenesulfonate)) doped microparticles that were coated successively with poly (allylamine hydrochloride) and poly (sodium 4-styrenesulfonate) by layer-by-layer technique. Ferrofluid was incorporated between the polyelectrolyte layers. CaCO3-PSS core was etched by incubation with EDTA yielding spherical MMC. The MMC were evaluated for various physicochemical, pharmaceutical parameters and magnetic properties. Surface morphology, crystallinity, particle size, zeta potential, encapsulation efficiency, loading capacity, drug release pattern, release kinetics and AC susceptibility studies revealed spherical particles of ~3 μm size were obtained with a net zeta potential of +24.5 mV, 56% encapsulation and 18.6% drug loading capacity, 96% of cumulative drug release obeyed Hixson-Crowell model release kinetics. Drug excipient interaction, surface area, thermal and storage stability studies for the prepared MMC was also evaluated. The developed MMC offer a promising mode of targeted and sustained release drug delivery for rheumatoid arthritis therapy.

  16. Design, synthesis, characterization and drug release kinetics of PAMAM dendrimer based drug formulations

    NASA Astrophysics Data System (ADS)

    Kurtoglu, Yunus Emre

    The drug release characteristics of G4-polyamidoamine (PAMAM) dendrimer-ibuprofen conjugates with ester, amide, and peptide linkers were investigated, in addition to a linear PEG-ibuprofen conjugate to understand the effect of architecture and linker on drug release. Ibuprofen was directly conjugated to NH2 -terminated dendrimer by an amide bond and OH-terminated dendrimer by an ester bond. A tetra-peptide linked dendrimer conjugate and a linear mPEG-ibuprofen conjugate were also studied for comparison to direct linked dendrimer conjugates. It is demonstrated that the 3-D nanoscale architecture of PAMAM dendrimer-drug conjugates, along with linking chemistry govern the drug release mechanisms as well as kinetics. Understanding these structural effects on their drug release characteristics is crucial for design of dendrimer conjugates with high efficacy such as poly(amidoamine) dendrimer-N-Acetylcysteine conjugates with disulfide linkages. N-Acetylcysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. A poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), Cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells using reactive oxygen species (ROS) assays. The conjugates showed an order of magnitude increase in anti-oxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.

  17. Rhamnogalacturonan-I Based Microcapsules for Targeted Drug Release

    PubMed Central

    Kusic, Anja; De Gobba, Cristian; Larsen, Flemming H.; Sassene, Philip; Zhou, Qi; van de Weert, Marco; Mullertz, Anette; Jørgensen, Bodil; Ulvskov, Peter

    2016-01-01

    Drug targeting to the colon via the oral administration route for local treatment of e.g. inflammatory bowel disease and colonic cancer has several advantages such as needle-free administration and low infection risk. A new source for delivery is plant-polysaccharide based delivery platforms such as Rhamnogalacturonan-I (RG-I). In the gastro-intestinal tract the RG-I is only degraded by the action of the colonic microflora. For assessment of potential drug delivery properties, RG-I based microcapsules (~1 μm in diameter) were prepared by an interfacial poly-addition reaction. The cross-linked capsules were loaded with a fluorescent dye (model drug). The capsules showed negligible and very little in vitro release when subjected to media simulating gastric and intestinal fluids, respectively. However, upon exposure to a cocktail of commercial RG-I cleaving enzymes, ~ 9 times higher release was observed, demonstrating that the capsules can be opened by enzymatic degradation. The combined results suggest a potential platform for targeted drug delivery in the terminal gastro-intestinal tract. PMID:27992455

  18. Photonic monitoring of chitosan nanostructured alginate microcapsules for drug release

    NASA Astrophysics Data System (ADS)

    Khajuria, Deepak Kumar; Konnur, Manish C.; Vasireddi, Ramakrishna; Roy Mahapatra, D.

    2015-02-01

    By using a novel microfluidic set-up for drug screening applications, this study examines delivery of a novel risedronate based drug formulation for treatment of osteoporosis that was developed to overcome the usual shortcomings of risedronate, such as its low bioavailability and adverse gastric effects. Risedronate nanoparticles were prepared using muco-adhesive polymers such as chitosan as matrix for improving the intestinal cellular absorption of risedronate and also using a gastric-resistant polymer such as sodium alginate for reducing the gastric inflammation of risedronate. The in-vitro characteristics of the alginate encapsulated chitosan nanoparticles are investigated, including their stability, muco-adhesiveness, and Caco-2 cell permeability. Fluorescent markers are tagged with the polymers and their morphology within the microcapsules is imaged at various stages of drug release.

  19. Water boiling inside carbon nanotubes: toward efficient drug release.

    PubMed

    Chaban, Vitaly V; Prezhdo, Oleg V

    2011-07-26

    We show using molecular dynamics simulation that spatial confinement of water inside carbon nanotubes (CNTs) substantially increases its boiling temperature and that a small temperature growth above the boiling point dramatically raises the inside pressure. Capillary theory successfully predicts the boiling point elevation down to 2 nm, below which large deviations between the theory and atomistic simulation take place. Water behaves qualitatively different inside narrow CNTs, exhibiting transition into an unusual phase, where pressure is gas-like and grows linearly with temperature, while the diffusion constant is temperature-independent. Precise control over boiling by CNT diameter, together with the rapid growth of inside pressure above the boiling point, suggests a novel drug delivery protocol. Polar drug molecules are packaged inside CNTs; the latter are delivered into living tissues and heated by laser. Solvent boiling facilitates drug release.

  20. Recent advances in chitosan films for controlled release of drugs.

    PubMed

    Mengatto, Luciano N; Helbling, Ignacio M; Luna, Julio A

    2012-08-01

    Chitosan is a versatile carrier for biologically active agent from a small molecule such as an antibiotic to macromolecules such as proteins and nucleic acids. In addition, drug delivery devices based on chitosan can be available in a variety of morphologies including films, fibers, nanoparticles and microspheres. Otherwise the inherent advantages of this polymer such as biocompatibility, tissue adhesions and hydrophilic nature, chitosan can be modified to accomplish a specific purpose, for example improves release kinetics. In this review, recent patents of chitosan-based film systems for drug delivery are presented and discussed. This review include matrix type systems, membrane coated systems and film forming solution. For each one of these systems, several examples of manufacture processes, bioactive agents to be delivered and specifics applications are considered. This work highlights the use of chitosan in the film technology for drug delivery, presenting examples of chitosan used in an unmodified state and examples of modifications of the polymer backbone.

  1. Factors affecting drug adsorption on beta zeolites.

    PubMed

    Pasti, Luisa; Sarti, Elena; Cavazzini, Alberto; Marchetti, Nicola; Dondi, Francesco; Martucci, Annalisa

    2013-05-01

    The adsorption behaviour of three commonly used drugs, namely ketoprofen, hydrochlorothiazide and atenolol, from diluted aqueous solutions on beta zeolites with different SiO2/Al2O3 ratio (i.e. 25, 38 and 360) was investigated by changing the ionic strength and the pH, before and after thermal treatment of the adsorbents. The selective adsorption of drugs was confirmed by thermogravimetry and X-ray diffraction. The adsorption capacity of beta zeolites was strongly dependent on both the solution pH and the alumina content of the adsorbent. Such a remarkable difference was interpreted as a function of the interactions between drug molecules and zeolite surface functional groups. Atenolol was readily adsorbed on the less hydrophobic zeolite, under pH conditions in which electrostatic interactions were predominant. On the other hand, ketoprofen adsorption was mainly driven by hydrophobic interactions. For undissociated molecules the adsorption capability increased with the increase of hydrophobicity.

  2. Utilizing the protein corona around silica nanoparticles for dual drug loading and release

    NASA Astrophysics Data System (ADS)

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-01

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration

  3. One-step fabrication of inorganic/organic hybrid microspheres with tunable surface texture for controlled drug release application.

    PubMed

    Dong, Hua; Tang, Guannan; Ma, Ting; Cao, Xiaodong

    2016-01-01

    In this paper, we report one-step fabrication of poly(lactide-co-glycolic acid)/titanium oxide (PLGA/TiO2) hybrid microspheres with tunable surface texture via droplet-based microfluidics. Surface texture of microspheres can be continuously tuned by changing the mass ratio between titanium tetraisopropoxide (TTIP) and PLGA in the dispersed phase. The fast hydrolysis of TTIP on the droplet surface can generate a thin shell membrane, resulting in a wrinkled surface after extraction of organic solvent. In vitro drug release monitoring of tanshinone IIA-loaded PLGA/TiO2 hybrid microsphere reveals that surface texture can affect the drug release rate to a large extent without sacrificing the drug encapsulation efficiency. Our finding might benefit the sustained drug delivery where variable drug release rate and high drug encapsulation efficiency are both required.

  4. Controlled drug release on amine functionalized spherical MCM-41

    SciTech Connect

    Szegedi, Agnes; Popova, Margarita; Goshev, Ivan; Klebert, Szilvia; Mihaly, Judit

    2012-10-15

    MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N{sub 2} physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin method and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41. - Graphical abstract: Determination of surface amino groups by ninhidrin method. Highlights: Black-Right-Pointing-Pointer Spherical MCM-41 modified by different amounts of APTES was studied. Black-Right-Pointing-Pointer Ibuprofen (IBU) adsorption and release characteristics was tested. Black-Right-Pointing-Pointer The ninhydrin reaction was used for the quantitative determination of amino groups. Black-Right-Pointing-Pointer Stoichiometric amount of APTES is enough for totally covering the surface with amino groups. Black-Right-Pointing-Pointer Good correlation was found between the amino content and IBU adsorption capacity.

  5. Polymer-surfactant nanoparticles for sustained release of water-soluble drugs.

    PubMed

    Chavanpatil, Mahesh D; Khdair, Ayman; Patil, Yogesh; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

    2007-12-01

    Poor drug encapsulation efficiency and rapid release of the encapsulated drug limit the use of nanoparticles in biomedical applications involving water-soluble drugs. We have developed a novel polymer-surfactant nanoparticle formulation, using the anionic surfactant Aerosol OT (AOT) and polysaccharide polymer alginate, for sustained release of water-soluble drugs. Particle size of nanoparticles, as determined by atomic force microscopy and transmission electron microscopy, was in the range of 40-70 nm. Weakly basic molecules like methylene blue, doxorubicin, rhodamine, verapamil, and clonidine could be encapsulated efficiently in AOT-alginate nanoparticles. In vitro release studies with basic drug molecules indicate that nanoparticles released 60-70% of the encapsulated drug over 4 weeks, with near zero-order release during the first 15 days. Studies with anionic drug molecules demonstrate poorer drug encapsulation efficiency and more rapid drug release than those observed with basic drugs. Further studies investigating the effect of sodium concentration in the release medium and the charge of the drug suggest that calcium-sodium exchange between nanoparticle matrix and release medium and electrostatic interaction between drug and nanoparticle matrix are important determinants of drug release. In conclusion, we have formulated a novel surfactant-polymer drug delivery carrier demonstrating sustained release of water-soluble drugs.

  6. Experimental design for optimizing drug release from silicone elastomer matrix and investigation of transdermal drug delivery.

    PubMed

    Snorradóttir, Bergthóra S; Gudnason, Pálmar I; Thorsteinsson, Freygardur; Másson, Már

    2011-04-18

    Silicone elastomers are commonly used for medical devices and external prosthesis. Recently, there has been growing interest in silicone-based medical devices with enhanced function that release drugs from the elastomer matrix. In the current study, an experimental design approach was used to optimize the release properties of the model drug diclofenac from medical silicone elastomer matrix, including a combination of four permeation enhancers as additives and allowing for constraints in the properties of the material. The D-optimal design included six factors and five responses describing material properties and release of the drug. The first experimental object was screening, to investigate the main and interaction effects, based on 29 experiments. All excipients had a significant effect and were therefore included in the optimization, which also allowed the possible contribution of quadratic terms to the model and was based on 38 experiments. Screening and optimization of release and material properties resulted in the production of two optimized silicone membranes, which were tested for transdermal delivery. The results confirmed the validity of the model for the optimized membranes that were used for further testing for transdermal drug delivery through heat-separated human skin. The optimization resulted in an excipient/drug/silicone composition that resulted in a cured elastomer with good tensile strength and a 4- to 7-fold transdermal delivery increase relative to elastomer that did not contain excipients.

  7. Magnetically Stimulated Release of a Model Drug From a Magnetic Drug Carrier

    NASA Astrophysics Data System (ADS)

    Riley, Tom; Evans, Ben

    The use of particles in the micro and nanometer ranges has become increasingly important as therapeutic tools in medicine. In particular, magnetically-active particles may allow for magnetically-controlled release of drugs at targeted locations. The drugs can be delivered directly to cancerous tumors at desired concentrations. While hydrogel-based microspheres have been commonly proposed for such purposes, there is also a need for a lipophilic magnetic microsphere for delivery of poorly-soluble pharmaceuticals. We have created a well-dispersed suspension of iron oxide nanoparticles in a silicone matrix, and have used the material to manufacture microspheres in sizes ranging from 100nm to 50 microns. Our spheres are stable in aqueous suspensions, yet their silicone matrix is uniquely suited for the transport and delivery of hydrophobic pharmaceuticals. A high concentration of magnetic nanoparticles (50% wt.) enables magnetic localization, magnetic heating (hyperthermia), and magnetic stimulation to trigger drug release. Using fluorescein as a model drug, we use UV-visible spectroscopy to show a slow native release rate of the hydrophobic fluorescein from the spheres. We use these measurements to quantify the loading capacity of the microspheres, and we show results of magnetically-stimulated drug release using a DM100 field applicator (nanoScale Biomagnetics).

  8. Immunomodulatory Drugs Regulate HMGB1 Release from Activated Human Monocytes

    PubMed Central

    Schierbeck, Hanna; Wähämaa, Heidi; Andersson, Ulf; Harris, Helena Erlandsson

    2010-01-01

    Several HMGB1-specific antagonists have provided beneficial results in multiple models of inflammatory disease–preclinical trials including arthritis. Since no HMGB1-specific targeted therapy has yet reached the clinic, we have performed in vitro studies to investigate whether any of a selection of well-established antirheumatic drugs inhibit HMGB1 release as part of its mode of action. Freshly purified peripheral blood monocytes from healthy donors were stimulated in cultures with LPS and IFNγ to cause HMGB1 and TNF release detected in ELISPOT assays. Effects on the secretion were assessed in cultures supplemented with dexamethasone, cortisone, chloroquine, gold sodium thiomalate, methotrexate, colchicine, etanercept or anakinra. Pharmacologically relevant doses of dexamethasone, gold sodium thiomalate and chloroquine inhibited the extracellular release of HMGB1 in a dose-dependent mode. Immunostaining demonstrated that dexamethasone caused intracellular HMGB1 retention. No effects on HMGB1 secretion were observed in cultures with activated monocytes by any of the other studied agents. TNF production in LPS/IFNγ-activated monocytes was readily downregulated by dexamethasone and, to some extent, by chloroquine and etanercept. We conclude that dexamethasone, gold sodium thiomalate and chloroquine share a capacity to inhibit HMGB1 release from activated monocytes. PMID:20386869

  9. Mathematical modeling of triamcinolone acetonide drug release from the I-vation intravitreal implant (a controlled release platform).

    PubMed

    Barnett, Peter J

    2009-01-01

    In-vitro drug release of triamcinolone acetonide from the I-vation implant can be controlled and tuned by varying its formulation ingredients. These release characteristics can be modeled using a parabolic partial differential equation to describe one dimensional Fickian drug diffusion in a durable polymer matrix.

  10. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

    PubMed

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.

  11. Factors affecting the pharmacokinetics and pharmacodynamics of liposomal drugs.

    PubMed

    Song, Gina; Wu, Huali; Yoshino, Keisuke; Zamboni, William C

    2012-09-01

    Various attempts to increase the therapeutic index of the drug while minimizing side effects have been made in drug delivery systems. Among several promising strategies, liposomes represent an advanced technology to target active molecules to the site of action. Rapid clearance of circulating liposomal drugs administered intravenously has been a critical issue because circulation time in the blood affects drug exposure at the target site. The clinical use of liposomal drugs is complicated by large intra- and interindividual variability in their pharmacokinetics (PK) and pharmacodynamics (PD). Thus, it is important to understand the factors affecting the PK/PD of the liposomal formulation of drugs and to elucidate the mechanisms underlying the variability in the PK/PD of liposomal drugs. In this review article, we describe the characteristics of liposome formulations and discuss the effects of various factors, including liposome-associated factors, host-associated factors, and treatment on the PK/PD of liposomal agents.

  12. In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices.

    PubMed

    Zhang, J; Wang, Q; Wang, A

    2010-02-01

    In order to find a new way to slow down the release of drugs and to solve the burst release problem of drugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium alginate/hydroxyapatite (SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in the beads during the sol-gel transition process of SA. The SA/HA nanocomposites were characterized by Fourier transform IR spectroscopy, X-ray fluorescence spectrometry, scanning electron microscopy and field emission SEM in order to reveal their composition and surface morphology as well as the role that the in situ generated HA micro-particles play. The factors influencing the swelling behavior, drug loading and controlled release behavior of the SA/HA nanocomposite beads were also investigated using diclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the nanocomposites, which could contract and restrict the movability of the SA polymer chains, and then change the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency of DS was improved, and the burst release of DS was overcome. The factors (including concentration of Ca(2+), reaction time and temperature) affecting the growth of HA micro-particles have a clear influence on the entrapment efficiency and release rate of DS. In this work, the nanocomposite beads prepared under optimum condition could prolong the release of DS for 8h more compared with the pristine SA hydrogel beads.

  13. A Fibrous Localized Drug Delivery Platform with NIR-Triggered and Optically Monitored Drug Release.

    PubMed

    Liu, Heng; Fu, Yike; Li, Yangyang; Ren, Zhaohui; Li, Xiang; Han, Gaorong; Mao, Chuanbin

    2016-09-06

    Implantable localized drug delivery systems (LDDSs) with intelligent functionalities have emerged as a powerful chemotherapeutic platform in curing cancer. Developing LDDSs with rationally controlled drug release and real-time monitoring functionalities holds promise for personalized therapeutic protocols but suffers daunting challenges. To overcome such challenges, a series of porous Yb(3+)/Er(3+) codoped CaTiO3 (CTO:Yb,Er) nanofibers, with specifically designed surface functionalization, were synthesized for doxorubicin (DOX) delivery. The content of DOX released could be optically monitored by increase in the intensity ratio of green to red emission (I550/I660) of upconversion photoluminescent nanofibers under 980 nm near-infrared (NIR) excitation owing to the fluorescence resonance energy transfer (FRET) effect between DOX molecules and the nanofibers. More importantly, the 808 nm NIR irradiation enabled markedly accelerated DOX release, confirming representative NIR-triggered drug release properties. In consequence, such CTO:Yb,Er nanofibers presented significantly enhanced in vitro anticancer efficacy under NIR irradiation. This study has thus inspired another promising fibrous LDDS platform with NIR-triggered and optics-monitored DOX releasing for personalized tumor chemotherapy.

  14. A Fibrous Localized Drug Delivery Platform with NIR-Triggered and Optically Monitored Drug Release

    PubMed Central

    Liu, Heng; Fu, Yike; Li, Yangyang; Ren, Zhaohui; Li, Xiang; Han, Gaorong; Mao, Chuanbin

    2016-01-01

    Implantable localized drug delivery systems (LDDSs) with intelligent functionalities have emerged as a powerful chemotherapeutic platform in curing cancer. Developing LDDSs with rationally controlled drug release and real-time monitoring functionalities holds promise for personalized therapeutic protocols but suffers daunting challenges. To overcome such challenges, a series of porous Yb3+/Er3+ codoped CaTiO3 (CTO:Yb,Er) nanofibers, with specifically designed surface functionalization, were synthesized for doxorubicin (DOX) delivery. The content of DOX released could be optically monitored by increase in the intensity ratio of green to red emission (I550/I660) of upconversion photoluminescent nanofibers under 980 nm near-infrared (NIR) excitation owing to the fluorescence resonance energy transfer (FRET) effect between DOX molecules and the nanofibers. More importantly, the 808 nm NIR irradiation enabled markedly accelerated DOX release, confirming representative NIR-triggered drug release properties. In consequence, such CTO:Yb,Er nanofibers presented significantly enhanced in vitro anticancer efficacy under NIR irradiation. This study has thus inspired another promising fibrous LDDS platform with NIR-triggered and optics-monitored DOX releasing for personalized tumor chemotherapy. PMID:27557281

  15. Cyclodextrin-gated mesoporous silica nanoparticles as drug carriers for red light-induced drug release.

    PubMed

    Chai, Shiqiang; Guo, Yu; Zhang, Zhenyu; Chai, Zhen; Ma, Yurong; Qi, Limin

    2017-04-07

    Long wavelength light-responsive drug delivery systems based on mesoporous silica nanoparticles (MSNs) have attracted much attention in the last few years. In this paper, a red light (660 nm)-responsive drug delivery system based on low-cost cyclodextrin (CD)-gated MSNs containing a photodynamic therapy (PDT) photosensitizer (Chlorin e6, Ce6) was developed for the first time. The drug release experiment in water demonstrated that with the irradiation of red light, Ce6 can be excited to generate singlet oxygen, which can further cleave the singlet oxygen sensitive linker to trigger the departure of CD and the release of cargo. Further in vitro release experiments confirmed that cargo can be released from MSNs with the irradiation of red light and spread into the entire cell. The relative low power density (0.5 W cm(-2)) of excitation light together with the short irradiation time (one-three min) result in a low light dose (30-90 J cm(-2)) for the drug delivery, contributing to their potential clinical applications.

  16. Cyclodextrin-gated mesoporous silica nanoparticles as drug carriers for red light-induced drug release

    NASA Astrophysics Data System (ADS)

    Chai, Shiqiang; Guo, Yu; Zhang, Zhenyu; Chai, Zhen; Ma, Yurong; Qi, Limin

    2017-04-01

    Long wavelength light-responsive drug delivery systems based on mesoporous silica nanoparticles (MSNs) have attracted much attention in the last few years. In this paper, a red light (660 nm)-responsive drug delivery system based on low-cost cyclodextrin (CD)-gated MSNs containing a photodynamic therapy (PDT) photosensitizer (Chlorin e6, Ce6) was developed for the first time. The drug release experiment in water demonstrated that with the irradiation of red light, Ce6 can be excited to generate singlet oxygen, which can further cleave the singlet oxygen sensitive linker to trigger the departure of CD and the release of cargo. Further in vitro release experiments confirmed that cargo can be released from MSNs with the irradiation of red light and spread into the entire cell. The relative low power density (0.5 W cm‑2) of excitation light together with the short irradiation time (one–three min) result in a low light dose (30–90 J cm‑2) for the drug delivery, contributing to their potential clinical applications.

  17. A framework to investigate drug release variability arising from hypromellose viscosity specifications in controlled release matrix tablets.

    PubMed

    Mitchell, Shawn A; Balwinski, Karen M

    2008-06-01

    Substitution level, particle size, and molecular weight are key properties of hypromellose (HPMC) known to be important to its performance in pharmaceutical-controlled release applications. The hypromellose monographs indirectly specify acceptable ranges for the molecular weight of HPMC products, expressed as the apparent viscosity of a 2% aqueous solution. The purpose of this study was to provide a framework to systematically investigate the amount of drug release variability that might be expected for typical controlled release formulations over the monograph viscosity ranges for hypromellose. An approach to estimate the expected drug release variability was developed based on scaling laws in the literature. New experimental data were generated with pentoxifylline, theophylline, and hydrochlorothiazide as model drugs to explore the applicability of this approach to a range of formulations. This methodology predicted that drug release variability over the United States Pharmacopeia (USP) viscosity ranges would be greatest for the lower viscosity grades of hypromellose, such as E50 and K100 LV. Drug release variability due to hypromellose viscosity variations is expected to be larger for formulations having substantial contributions from erosional drug release, and smaller for formulations with a predominantly diffusional drug release mechanism. These predictions need to be validated experimentally.

  18. Utilizing the protein corona around silica nanoparticles for dual drug loading and release.

    PubMed

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-21

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.

  19. Impact of emulsion-based drug delivery systems on intestinal permeability and drug release kinetics.

    PubMed

    Buyukozturk, Fulden; Benneyan, James C; Carrier, Rebecca L

    2010-02-25

    Lipid based drug delivery systems, and in particular self-emulsifying drug delivery systems (SEDDS), show great potential for enhancing oral bioavailability but have not been broadly applied, largely due to lack of general formulation guidance. To help understand how formulation design influences physicochemical emulsion properties and associated function in the gastrointestinal environment, a range of twenty-seven representative self-emulsifying formulations were investigated. Two key functions of emulsion-based drug delivery systems, permeability enhancement and drug release, were studied and statistically related to three formulation properties - oil structure, surfactant hydrophilic liphophilic balance (HLB) values, and surfactant-to-oil ratio. Three surfactants with HLB values ranging from 10 to 15 and three structurally different oils (long chain triglyceride, medium chain triglyceride, and propylene glycol dicaprylate/dicaprate) were combined at three different weight ratios (1:1, 5:1, 9:1). Unstable formulations of low HLB surfactant (HLB=10) had a toxic effect on cells at high (1:1) surfactant concentrations, indicating the importance of formulation stability for minimizing toxicity. Results also indicate that high HLB surfactant (Tween 80) loosens tight junction at high (1:1) surfactant concentrations. Release coefficients for each emulsion system were calculated. Incorporation of a long chain triglyceride (Soybean oil) as the oil phase increased the drug release rate constant. These results help establish an initial foundation for relating emulsion function to formulation design and enabling bioavailability optimization across a broad, representative range of SEDDS formulations.

  20. Doxorubicin encapsulated in stealth liposomes conferred with light-triggered drug release.

    PubMed

    Luo, Dandan; Carter, Kevin A; Razi, Aida; Geng, Jumin; Shao, Shuai; Giraldo, Daniel; Sunar, Ulas; Ortega, Joaquin; Lovell, Jonathan F

    2016-01-01

    Stealth liposomes can be used to extend the blood circulation time of encapsulated therapeutics. Inclusion of 2 molar % porphyrin-phospholipid (PoP) imparted optimal near infrared (NIR) light-triggered release of doxorubicin (Dox) from conventional sterically stabilized stealth liposomes. The type and amount of PoP affected drug loading, serum stability and drug release induced by NIR light. Cholesterol and PEGylation were required for Dox loading, but slowed light-triggered release. Dox in stealth PoP liposomes had a long circulation half-life in mice of 21.9 h and was stable in storage for months. Following intravenous injection and NIR irradiation, Dox deposition increased ∼ 7 fold in treated subcutaneous human pancreatic xenografts. Phototreatment induced mild tumor heating and complex tumor hemodynamics. A single chemophototherapy treatment with Dox-loaded stealth PoP liposomes (at 5-7 mg/kg Dox) eradicated tumors while corresponding chemo- or photodynamic therapies were ineffective. A low dose 3 mg/kg Dox phototreatment with stealth PoP liposomes was more effective than a maximum tolerated dose of free (7 mg/kg) or conventional long-circulating liposomal Dox (21 mg/kg). To our knowledge, Dox-loaded stealth PoP liposomes represent the first reported long-circulating nanoparticle capable of light-triggered drug release.

  1. Effect of mechanical and electrical behavior of gelatin hydrogels on drug release and cell proliferation.

    PubMed

    Biswal, Dibyajyoti; Anupriya, B; Uvanesh, K; Anis, Arfat; Banerjee, Indranil; Pal, Kunal

    2016-01-01

    The present study was aimed to explore the effect of the mechanical and the electrical properties of the gelatin hydrogels on the mammalian cell proliferation and drug release properties. FTIR analysis of the hydrogels suggested that gelatin retained its secondary protein structure. A decrease in the diffusion constant of the water molecules was observed with the increase in the gelatin concentration in the hydrogels. The mechanical and the electrical stabilities of the hydrogels were enhanced with the increase in the gelatin content. Stress relaxation and creep studies were modeled using Weichert and Burger׳s models, respectively. The relaxation time (stress relaxation study) did not follow a concentration-dependent relationship and was found to affect the MG-63 cell (human osteoblast) proliferation. The impedance profile of the hydrogels was modeled using a (RQ)Q model. Release of ciprofloxacin from the hydrogels was inversely dependent on the rate of swelling. The release of the drug was not only dependent on the Fickian diffusion but also on the relaxation process of the gelatin chains. The inhomogeneous constant of the constant phase element representing the hydrogel-electrode interface indicated improved cell proliferation rate with a decrease in the inhomogeneous constant. In gist, the rate of cell proliferation could be related to the relaxation time (stress relaxation) and the inhomogeneous constant of the sample-electrode constant phase element (electrical study) properties, whereas, the drug release properties can be related to the bulk resistance of the formulations.

  2. Study of mesoporous silica/magnetite systems in drug controlled release.

    PubMed

    Souza, K C; Ardisson, J D; Sousa, E M B

    2009-02-01

    Ordered mesoporous materials like SBA-15 have a network of channels and pores with well-defined size in the nanoscale range. This particular silica matrix pore architecture makes them suitable for hosting a broad variety of compounds in very promising materials in a range of applications, including drug release magnetic carriers. In this work, magnetic nanoparticles embedded into mesoporous silica were prepared in two steps: first, magnetite was synthesized by oxidation-precipitation method, and next, the magnetic nanoparticles were coated with mesoporous silica by using nonionic block copolymer surfactants as structure-directing agents. The materials were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), N(2) adsorption, and scanning electron microscopy (SEM). The influence of magnetic nanoparticles on drug release kinetics was studied with cisplatin, carboplatin, and atenolol under in vitro conditions in the absence and in the presence of an external magnetic field (0.25 T) by using NdFeB permanent magnet. The constant external magnetic field did not affect drug release significantly. The low-frequency alternating magnetic field had a large influence on the cisplatin release profile.

  3. The drug release study of ceftriaxone from porous hydroxyapatite scaffolds.

    PubMed

    Al-Sokanee, Zeki N; Toabi, Abedl Amer H; Al-Assadi, Mohammed J; Alassadi, Erfan A S

    2009-01-01

    Hydroxyapatite (HAP) is an important biomedical material that is used for grafting osseous defects. It has an excellent bioactivity and biocompatibility properties. To isolate hydroxyapatite, pieces of cleaned cattle's bone were heated at different temperature range from 400 degrees C up to 1,200 degrees C. A reasonable yield of 60.32% w/w HAP was obtained at temperature range from 1,000 degrees C to 1,200 degrees C. Fourier transform infrared spectra and the thermogravimetric measurement showed a clear removal of organic at 600 degrees C as well as an excellent isolation of HAP from the bones which was achieved at 1,000-1,200 degrees C. This was also confirmed from X-ray diffraction of bone sample heated at 1,200 degrees C. The concentration ions were found to be sodium, potassium, lithium, zinc, copper, iron, calcium, magnesium, and phosphate present in bones within the acceptable limits for its role in the bioactivity property of HAP. Glucose powder was used as a porosifier. Glucose was novel and excellent as porogen where it was completely removed by heating, giving an efficient porosity in the used scaffolds. The results exhibited that the ceftriaxone drug release was increased with increasing the porosity. It was found that a faster, higher, and more regular drug release was obtained from the scaffold with a porosity of 10%.

  4. Kinetics of drug release from ointments: Role of transient-boundary layer.

    PubMed

    Xu, Xiaoming; Al-Ghabeish, Manar; Krishnaiah, Yellela S R; Rahman, Ziyaur; Khan, Mansoor A

    2015-10-15

    In the current work, an in vitro release testing method suitable for ointment formulations was developed using acyclovir as a model drug. Release studies were carried out using enhancer cells on acyclovir ointments prepared with oleaginous, absorption, and water-soluble bases. Kinetics and mechanism of drug release was found to be highly dependent on the type of ointment bases. In oleaginous bases, drug release followed a unique logarithmic-time dependent profile; in both absorption and water-soluble bases, drug release exhibited linearity with respect to square root of time (Higuchi model) albeit differences in the overall release profile. To help understand the underlying cause of logarithmic-time dependency of drug release, a novel transient-boundary hypothesis was proposed, verified, and compared to Higuchi theory. Furthermore, impact of drug solubility (under various pH conditions) and temperature on drug release were assessed. Additionally, conditions under which deviations from logarithmic-time drug release kinetics occur were determined using in situ UV fiber-optics. Overall, the results suggest that for oleaginous ointments containing dispersed drug particles, kinetics and mechanism of drug release is controlled by expansion of transient boundary layer, and drug release increases linearly with respect to logarithmic time.

  5. Drug release behavior of chitosan-montmorillonite nanocomposite hydrogels following electrostimulation.

    PubMed

    Liu, Kun-Ho; Liu, Ting-Yu; Chen, San-Yuan; Liu, Dean-Mo

    2008-07-01

    Nanocomposites hydrogel (nanohydrogel) composed of chitosan (CS) and montmorillonite (MMT) were prepared and systematically studied for drug release behavior following electrostimulation. The deterioration of the responsiveness and reversibility of CS upon repeated on-off electrostimulation switching operations are major limitations for clinical applications, as it suffers from too much structural instability for the precise control of the release of drug upon cyclic electrostimulation. To overcome these limitations, an inorganic phase, MMT, was incorporated in the CS matrix to enhance the anti-fatigue property and corresponding long-term stable release kinetics. X-ray diffraction analysis and time-dependent optical absorbance showed that the MMT incorporated into the nanohydrogel exhibited an exfoliated nanostructure. The exfoliated silica nanosheets are able to act as cross-linkers to form a network structure between the CS and MMT, and this difference in the cross-linking density strongly affects the release of vitamin B(12) under electrostimulation. With a lower MMT concentration (1 wt.%), the release kinetics of vitamin B(12) from the nanohydrogel shows a pseudo-zero-order release, and the release mechanism was changed from a diffusion-controlled mode to a swelling-controlled mode under electrostimulation. Further increasing the MMT content reduced both the diffusion exponent n and the responsiveness of the nanohydrogel to electrostimulation. In addition, a consecutively repeated "on" and "off" operation shows that the electroresponsiveness of the nanohydrogel with higher MMT concentrations was reduced, but its anti-fatigue behavior was considerably improved. In this work, the nanohydrogel with 2 wt.% MMT achieved a mechanically reliable and practically desirable pulsatile release profile and excellent anti-fatigue behavior, compared with that of the pure CS.

  6. A novel drug carrier based on functional modified nanofiber cellulose and the control release behavior

    NASA Astrophysics Data System (ADS)

    Shi, Xiangning; Zheng, Yudong; Zhang, Wei; Zhang, Zeyu; Peng, Yunling

    2013-08-01

    This study developed a novel drug carrier based on functional modified bacterial cellulose(BC) which was conjugated with Ibuprofen(IBU) by esterification. BC-Ibuprofen as the macro- molecular prodrugs and drug carrier used to improve the short half-life of the drug, and was able to control release through the hydrolysis of ester bond between the hydroxyl groups of BC with Ibuprofen under different condition. Fourier transform infrared analysis revealed that Ibuprofen had been successfully grafted onto the bacterial cellulose (BC). Thermal and morphological characterization indicated the formation of the BC-Ibuprofen system incompletely reacted maintained the bulk structure of the pristine material such as crystallinity, 3-dimentional network and so on. The drug release behaviours were affected by the ester bond hydrolysis as well as the microstructure characteristics of the modified nanofiber. The release of BC-IBU showed an apparent pH-dependent, fast in alkaline and acid solution but slow relatively in neutral. Such pH-responsiveness, in addition to its morphological characteristics, in this paper suggested a great potential of BC-IBU as a more effective, safe, and stable prodrug candidate.

  7. Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms.

    PubMed

    Lin, Zhongqiang; Zhou, Deliang; Hoag, Stephen; Qiu, Yihong

    2016-03-01

    Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory

  8. Characterizing the Network of Drugs and Their Affected Metabolic Subpathways

    PubMed Central

    Li, Jing; Han, Junwei; Wang, Shuyuan; Yao, Qianlan; Wang, Yingying; Zhang, Yunpeng; Zhang, Chunlong; Xu, Yanjun; Jiang, Wei; Li, Xia

    2012-01-01

    A fundamental issue in biology and medicine is illustration of the overall drug impact which is always the consequence of changes in local regions of metabolic pathways (subpathways). To gain insights into the global relationship between drugs and their affected metabolic subpathways, we constructed a drug–metabolic subpathway network (DRSN). This network included 3925 significant drug–metabolic subpathway associations representing drug dual effects. Through analyses based on network biology, we found that if drugs were linked to the same subpathways in the DRSN, they tended to share the same indications and side effects. Furthermore, if drugs shared more subpathways, they tended to share more side effects. We then calculated the association score by integrating drug-affected subpathways and disease-related subpathways to quantify the extent of the associations between each drug class and disease class. The results showed some close drug–disease associations such as sex hormone drugs and cancer suggesting drug dual effects. Surprisingly, most drugs displayed close associations with their side effects rather than their indications. To further investigate the mechanism of drug dual effects, we classified all the subpathways in the DRSN into therapeutic and non-therapeutic subpathways representing drug therapeutic effects and side effects. Compared to drug side effects, the therapeutic effects tended to work through tissue-specific genes and these genes tend to be expressed in the adrenal gland, liver and kidney; while drug side effects always occurred in the liver, bone marrow and trachea. Taken together, the DRSN could provide great insights into understanding the global relationship between drugs and metabolic subpathways. PMID:23112813

  9. Controlled release of cortisone drugs from block copolymers synthetized by ATRP

    NASA Astrophysics Data System (ADS)

    Valenti, G.; La Carta, S.; Mazzotti, G.; Rapisarda, M.; Perna, S.; Di Gesù, R.; Giorgini, L.; Carbone, D.; Recca, G.; Rizzarelli, P.

    2016-05-01

    Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient's compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye's diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10-60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy (1H-NMR, 13C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different kinetic

  10. Factors That Affect Adolescent Drug Users' Suicide Attempts.

    PubMed

    Park, Subin; Song, Hokwang

    2016-05-01

    Drug abuse has been widely linked to suicide risk. We examined the factors that affect adolescent drug users' suicide attempts in South Korea. This study analyzed the data of 311 adolescents who had used drugs such as inhalants, psychotropic drugs, and marijuana (195 males and 116 females). Among 311 subjects, 109 (35.0%) had attempted suicide during the last 12 months. After adjusting for other variables, depressive mood (OR=19.79) and poly-drug use (OR=2.79), and low/middle levels of academic achievement compared with a high level (OR=3.72 and 4.38) were independently associated with increased odds of a suicide attempt, while better perceived health (OR=0.32) was independently associated with reduced odds of a suicide attempt. For adolescent drug users, preventive work should be directed toward the active treatment of drug use, depression, and physical health and reinforcing proper coping strategies for academic and other stress.

  11. Measure your septa release ratios: pheromone release ratio variability affected by rubber septa and solvent

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The type of solvent and volume of the solvent used to load pheromone/volatile components onto rubber septa had significant effects on release ratios, the variability of those release ratios, and the recoverability of the volatile components during subsequent extraction with hexane. Volatile release ...

  12. Oral self-nanoemulsifying peptide drug delivery systems: impact of lipase on drug release.

    PubMed

    Mahjub, Reza; Dorkoosh, Farid Abedin; Rafiee-Tehrani, Morteza; Bernkop Schnürch, Andreas

    2015-01-01

    It was the aim of this study to evaluate the impact of lipases on the release behaviour of a peptide drug from oral self-nanoemulsifying drug delivery systems. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate, oleate and dodecylsulphate. The lipophilic character of these complexes was characterised by determining the n-octanol/buffer pH 7.4 partition coefficient. In the following the most hydrophilic complex was incorporated in a likely lipase degradable self-nanoemulsifying drug delivery systems (SNEDDS) formulation containing a triglyceride (olive oil; Pharm.Eur.) and in a likely not lipase degradable SNEDDS containing lipids and surfactants without any ester bonds. After 1:100 dilutions in artificial intestinal fluid (AIF), the lipid droplets were characterised regarding size distribution. With these SNEDDS, drug release studies were performed in AIF with and without lipase. Results showed that the most hydrophobic complex can be formed with deoxycholate in an octreotide:anionic surfactant ratio of 1:5. Even 73.1 ± 8.1% of it could be quantified in the n-octanol phase. SNEDDS containing octreotide | olive oil | cremophor EL | propylene glycol (2|57|38|3) and octreotide | liquid paraffin | Brij 35 | propylene glycol | ethanol (2|66.5|25|5|1.5) showed after dilution in AIF, a mean droplet size of 232 ± 53 nm and 235 ± 50 nm, respectively. Drug release studies showed a sustained release of octreotide out of these formulations for at least 24 h, whereas > 80% of the drug was released within 2 h in the presence of lipase in the case of the triglyceride containing SNEEDS. In contrast the release profile from ester-free SNEDDS was not significantly altered (p < 0.05) due to the addition of lipase providing evidence for the stability of this formulation towards lipases. According to these results, SNEDDS could be identified as a useful tool for sustained oral peptide delivery taking an enzymatic degradation by

  13. Programmable release of multiple protein drugs from aptamer-functionalized hydrogels via nucleic acid hybridization.

    PubMed

    Battig, Mark R; Soontornworajit, Boonchoy; Wang, Yong

    2012-08-01

    Polymeric delivery systems have been extensively studied to achieve localized and controlled release of protein drugs. However, it is still challenging to control the release of multiple protein drugs in distinct stages according to the progress of disease or treatment. This study successfully demonstrates that multiple protein drugs can be released from aptamer-functionalized hydrogels with adjustable release rates at predetermined time points using complementary sequences (CSs) as biomolecular triggers. Because both aptamer-protein interactions and aptamer-CS hybridization are sequence-specific, aptamer-functionalized hydrogels constitute a promising polymeric delivery system for the programmable release of multiple protein drugs to treat complex human diseases.

  14. Long-term Controlled Drug Release from bi-component Electrospun Fibers

    NASA Astrophysics Data System (ADS)

    Xu, Shanshan; Zhang, Zixin; Xia, Qinghua; Han, Charles

    Multi-drug delivery systems with timed programmed release are hard to be produced due to the complex drug release kinetics which mainly refers to the diffusion of drug molecules from the fiber and the degradation of the carrier. This study focused on the whole life-time story of the long-term drug releasing fibrous systems. Electrospun membrane utilizing FDA approved polymers and broad-spectrum antibiotics showed specific drug release profiles which could be divided into three stages based on the profile slope. With throughout morphology observation, cumulative release amount and releasing duration, releasing kinetics and critical factors were fully discussed during three stages. Through changing the second component, approximately linear drug release profile and a drug release duration about 13 days was prepared, which is perfect for preventing post-operative infection. The addition of this semi-crystalline polymer in turn influenced the fiber swelling and created drug diffusion channels. In conclusion, through adjusting and optimization of the blending component, initial burst release, delayed release for certain duration, and especially the sustained release profile could all be controlled, as well as specific anti-bacterial behavior could be obtained.

  15. Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion.

    PubMed

    Pimenta, A F R; Ascenso, J; Fernandes, J C S; Colaço, R; Serro, A P; Saramago, B

    2016-12-30

    Optimization of drug delivery from drug loaded contact lenses assumes understanding the drug transport mechanisms through hydrogels which relies on the knowledge of drug partition and diffusion coefficients. We chose, as model systems, two materials used in contact lens, a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone based hydrogel, and three drugs with different sizes and charges: chlorhexidine, levofloxacin and diclofenac. Equilibrium partition coefficients were determined at different ionic strength and pH, using water (pH 5.6) and PBS (pH 7.4). The measured partition coefficients were related with the polymer volume fraction in the hydrogel, through the introduction of an enhancement factor following the approach developed by the group of C. J. Radke (Kotsmar et al., 2012; Liu et al., 2013). This factor may be decomposed in the product of three other factors EHS, Eel and Ead which account for, respectively, hard-sphere size exclusion, electrostatic interactions, and specific solute adsorption. While EHS and Eel are close to 1, Ead>1 in all cases suggesting strong specific interactions between the drugs and the hydrogels. Adsorption was maximal for chlorhexidine on the silicone based hydrogel, in water, due to strong hydrogen bonding. The effective diffusion coefficients, De, were determined from the drug release profiles. Estimations of diffusion coefficients of the non-adsorbed solutes D=De×Ead allowed comparison with theories for solute diffusion in the absence of specific interaction with the polymeric membrane.

  16. Local drug delivery - the early Berlin experience: single drug administration versus sustained release.

    PubMed

    Speck, Ulrich; Scheller, Bruno; Rutsch, Wolfgang; Laule, Michael; Stangl, Verena

    2011-05-01

    Our initial investigations into restenosis inhibition by local drug delivery were prompted by reports on an improved outcome of coronary interventions, including a lower rate of target lesion revascularisation, when the intervention was performed with an ionic instead of non-ionic contrast medium. Although this was not confirmed in an animal study, the short exposure of the vessel wall to paclitaxel dissolved in contrast agent or coated on balloons proved to be efficacious. A study comparing three methods of local drug delivery to the coronary artery in pigs indicated the following order of efficacy in inhibiting neointimal proliferation: paclitaxel-coated balloons > sirolimus-eluting stents, sustained drug release > paclitaxel in contrast medium. Cell culture experiments confirmed that cell proliferation can be inhibited by very short exposure to the drug. Shorter exposure times require higher drug concentrations. Effective paclitaxel concentrations in porcine arteries are achieved when the drug is dissolved in contrast medium or coated on balloons. Paclitaxel is an exceptional drug in that it stays in the treated tissue for a long time. This may explain the long-lasting efficacy of paclitaxel-coated balloons, but does not disprove the hypothesis that the agent blocks a process initiating long-lasting excessive neointimal proliferation, which occurs early after vessel injury.

  17. Double loaded self-decomposable SiO₂ nanoparticles for sustained drug release.

    PubMed

    Zhao, Saisai; Zhang, Silu; Ma, Jiang; Fan, Li; Yin, Chun; Lin, Ge; Li, Quan

    2015-10-21

    Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms-the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the "grown-in" drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window-a sustained drug delivery system with a great impact on improving the management of chronic diseases.

  18. INVESTIGATION OF DRUG RELEASE FROM BIODEGRADABLE PLG MICROSPHERES: EXPERIMENT AND THEORY

    SciTech Connect

    ANDREWS, MALCOLM J.; BERCHANE, NADER S.; CARSON, KENNETH H.; RICE-FICHT, ALLISON C.

    2007-01-30

    Piroxicam containing PLG microspheres having different size distributions were fabricated, and in vitro release kinetics were determined for each preparation. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the system size was increased. The mathematical model gave a good fit to the experimental release data.

  19. Electrospinning: methods and development of biodegradable nanofibres for drug release.

    PubMed

    Ashammakhi, N; Wimpenny, I; Nikkola, L; Yang, Y

    2009-02-01

    It is clear that nanofibrous structures can be used as tools for many applications. It is already known that electrospinning is a highly versatile method of producing nanofibres and recent developments in the technique of electrospinning have led to the development of aligned nanofibres and biphasic, core-sheath fibres which can be used to encapsulate different materials from molecules to cells. Natural extracellular matrix (ECM) contains fibres in both micro and nano-scales and provides a structural scaffold which allows cells to localize, migrate, proliferate and differentiate. Polymer nanofibres can provide the structural cues of ECM. However, current literature gives new hope to further functionalising polymeric nanofibres by using them for drug delivery devices and improving their design to improve control of delivery. By encapsulating active agents within nanofibres (multifunctional nanofibres), a degree of control can be exerted over the release of encapsulated agents and therefore, the behaviour of cells can be manipulated for developing effective therapies and is extremely encouraging in the tissue engineering field by combining factors like fibre diameter, alignment and chemicals in new ways. Such multifunctional nanofibre-based systems are already being investigated in vivo. Experiments have shown the significant potential for treatments of disease and engineering of neural and bone tissues. Further, phase III clinical trials of nanofibrous patches for applications in wound treatment were encouraging. Hopefully, clinical applications of these drug delivery devices will follow, to enhance regenerative medicine applications.

  20. Drug-sensing hydrogels for the inducible release of biopharmaceuticals

    NASA Astrophysics Data System (ADS)

    Ehrbar, Martin; Schoenmakers, Ronald; Christen, Erik H.; Fussenegger, Martin; Weber, Wilfried

    2008-10-01

    Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function. Transferring the knowledge of pharmacologically triggered protein-protein interactions to materials science will enable novel design concepts for stimuli-sensing smart hydrogels. Here, we show the design and validation of an antibiotic-sensing hydrogel for the trigger-inducible release of human vascular endothelial growth factor. Genetically engineered bacterial gyrase subunit B (GyrB) (ref. 4) coupled to polyacrylamide was dimerized by the addition of the aminocoumarin antibiotic coumermycin, resulting in hydrogel formation. Addition of increasing concentrations of clinically validated novobiocin (Albamycin) dissociated the GyrB subunits, thereby resulting in dissociation of the hydrogel and dose- and time-dependent liberation of the entrapped protein pharmaceutical VEGF121 for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient.

  1. Effects of implant diameter, drug loading and end-capping on praziquantel release from PCL implants.

    PubMed

    Li, Changyan; Cheng, Liang; Zhang, Yaqiong; Guo, Shengrong; Wu, Weiping

    2010-02-15

    Praziquantel (PZQ)-loaded poly(epsilon-caprolactone) (PCL) cylindrical implants were fabricated and characterized. Implant diameter (3, 4 and 8mm), drug loading (25% and 50%), and the end-capping were investigated to evaluate their effects on drug release. The evolution of implants with release time was conducted in terms of implant microstructure, crystallinity, drug content and molecular weight of PCL. The results showed that drug release was fastest for the implant with a diameter of 3mm and slowest for the implant with a diameter of 8mm; drug release from the implant with a drug content of 50% was faster than that from the implant with a drug content of 25%; the release of PZQ from the end-capped implants was slightly slower than that from the corresponding end-uncapped implants. The effect of drug loadings on PZQ release was related with diameter of the implants and the effect was weakened as diameter of the implants increased. The drug release data for all the implants were best fitted with Ritger-Peppas model, therefore Fickian diffusion was the predominant release mechanism. The evolution of implants with release time verified that PZQ was gradually released from the exterior to the interior of the implants.

  2. Multifunctional Hybrid Nanoparticles for Traceable Drug Delivery and Intracellular Microenvironment-Controlled Multistage Drug-Release in Neurons.

    PubMed

    Shi, Bingyang; Du, Xin; Chen, Jian; Fu, Libing; Morsch, Marco; Lee, Albert; Liu, Yong; Cole, Nicholas; Chung, Roger

    2017-03-31

    Innovative nanoparticles hold promising potential for disease therapy as drug delivery systems. For brain-disease therapy, a drug delivery system that can sustainably control drug-release and monitor fluorescence of the drug cargos is highly desirable. In this study, a light-traceable and intracellular microenvironment-responsive drug delivery system was developed based on the combination of glutathione-responsive autoflurescent nanogel, dendrimer-like mesoporous silica nanoparticles, and gold nanoparticles. The resulting hybrid nanoparticles represent a new class of delivery system that can efficiently load, transport, and control multistage-release of sulfydryl-containing drugs into neurons, with light-traceable monitoring for future brain-disease therapy.

  3. Effect of carboxymethylation on rheological and drug release characteristics of locust bean gum matrix tablets.

    PubMed

    Chakravorty, Amrita; Barman, Gouranga; Mukherjee, Sudipta; Sa, Biswanath

    2016-06-25

    This study was undertaken to investigate correlation between the carboxymethylation-induced rheological changes and drug release characteristics of locust bean gum (LBG) matrix tablets. LBG was derivatized to carboxymethyl LBG (CMLBG) and characterized by (13)C NMR, FTIR and elemental analyses. Rheological studies revealed that LBG, in contact with water, produced a strong elastic gel which swelled less due to lower penetration of water resulting in slower drug release. On the other hand, CMLBG formed a viscous polymer solution through which higher influx of water resulted in rapid swelling of the matrix and faster drug release. Although the release from a particular matrix was dependent on drugs' solubilities, CMLBG matrix tablet produced faster release of all the drugs than LBG matrix tablets. In conclusion, rheological study appeared to be an useful tool to predict release of drugs from polysaccharide matrix tablets.

  4. Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

    PubMed

    Khodaverdi, Elham; Soleimani, Hossein Ali; Mohammadpour, Fatemeh; Hadizadeh, Farzin

    2016-06-01

    Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment.

  5. About the effect of eye blinking on drug release from pHEMA-based hydrogels: an in vitro study.

    PubMed

    Galante, R; Paradiso, P; Moutinho, M G; Fernandes, A I; Mata, J L G; Matos, A P A; Colaço, R; Saramago, B; Serro, A P

    2015-01-01

    The development of new ophthalmic drug delivery systems capable of increasing the residence time of drugs in the eye and improve its bioavailability relatively to eyedrops has been object of intense research in recent years. Several studies have shown that drug-loaded therapeutic soft contact lenses (SCLs) constitute a promising approach, with several potential advantages as compared with collyria. The main objective of this work is to study the effect of repetitive load and friction cycles caused by the eye blinking, on the drug release from hydrogels used in SCLs which, as far as we know, was never investigated before. Two poly-2-hydroxyethylmethacrylate-based hydrogels, pHEMA-T and pHEMA-UV, were used as model materials. Levofloxaxin was chosen as model drug. The hydrogels were fully characterized in what concerns structural and physicochemical properties. pHEMA-UV revealed some superficial porosity and a lower short-range order than pHEMA-T. We observe that the load and friction cycles enhanced the drug release from pHEMA-UV hydrogels. The application of a simple mathematical model, which takes into account the drug dilution caused by the tear flow, showed that the enhancement of the drug release caused by blinking on this hydrogel may be relevant in in vivo conditions. Conversely, the more sustained drug release from pHEMA-T is not affected by load and friction cycles. The conclusion is that, depending on the physicochemical and microstructural characteristics of the hydrogels, blinking is a factor that may affect the amount of drug delivered to the eye by SCLs and should thus be considered.

  6. Quantitative ToF-SIMS Studies of Protein Drug Release from Biodegradable Polymer Drug Delivery Membranes

    PubMed Central

    Burns, Sarah A.; Gardella, Joseph A.

    2008-01-01

    Biodegradable polymers are of interest in developing strategies to control protein drug delivery. The protein that was used in this study is Keratinocyte Growth Factor (KGF) which is a protein involved in the re-epithelialization process. The protein is stabilized in the biodegradable polymer matrix during formulation and over the course of polymer degradation with the use of an ionic surfactant Aerosol-OT (AOT) which will encapsulate the protein in an aqueous environment. The release kinetics of the protein from the surface of these materials requires precise timing which is a crucial factor in the efficacy of this drug delivery system. Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) was used in the same capacity to identify the molecular ion peak of the surfactant and polymer and use this to determine surface concentration. In the polymer matrix, the surfactant molecular ion peak was observed in the positive and negative mode at m/z 467 and 421, respectively. These peaks were determined to be [AOT + Na+] and [AOT−Na+]-. These methods are used to identify the surfactant and protein from the polymer matrix and are used to measure the rate of surface accumulation. The second step was to compare this accumulation rate with the release rate of the protein into an aqueous solution during the degradation of the biodegradable film. This rate is compared to that from fluorescence spectroscopy measurements using the protein autofluorescence from that released into aqueous solution. PMID:20016666

  7. 77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... HUMAN SERVICES Food and Drug Administration Single-Ingredient, Immediate-Release Drug Products... AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug... such products in interstate commerce. The document was published with an incorrect Web link....

  8. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... approved new animal drug application, or listed in the index, as required by paragraph (a) of this section... of such articles. A new animal drug application or index listing is required in any such case. (d... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Timed-release dosage form drugs. 500.26...

  9. A mathematical model to predict the release of water-soluble drugs from HPMC matrices.

    PubMed

    Fu, X C; Wang, G P; Fu, C Y; Liang, W Q

    2004-09-01

    A mathematical model to predict the fraction of water-soluble drug released as a function of release time (t, h), HPMC concentration (CH, w/w), and volume of drug molecule (V, nm3) was derived with ranitidine hydrochloride, diltiazem hydrochloride, and ribavirin as model drugs. The model is log (M(t)/M(infinity)) = 0.5 log t-0.3322CH-0.2222V-0.2988 (n = 140, r = 0.9848), where M(t) is the amount of drug released at time t, M(infinity) is the amount of drug released over a very long time, which corresponds in principle to the initial loading, n is the number of samples, and r is the correlation coefficient. The model was validated using isoniazid and satisfactory results were obtained. The model can be used to predict the release fraction of various soluble drugs from HPMC matrices having different polymer levels.

  10. Pickering w/o emulsions: drug release and topical delivery.

    PubMed

    Frelichowska, Justyna; Bolzinger, Marie-Alexandrine; Valour, Jean-Pierre; Mouaziz, Hanna; Pelletier, Jocelyne; Chevalier, Yves

    2009-02-23

    The skin absorption from Pickering emulsions as a new dosage form was investigated for the first time. Pickering emulsions are stabilized by adsorbed solid particles instead of emulsifier molecules. They are promising dosage forms that significantly differ from classical emulsions within several features. The skin permeation of a hydrophilic model penetrant (caffeine) was investigated from a w/o Pickering emulsion and compared to a w/o classical emulsion stabilized with an emulsifier. Both emulsions had the same composition and physicochemical properties in order to focus on the effect of the interfacial layer on the drug release and skin absorption processes. The highest permeation rates were obtained from the Pickering emulsion with a pseudo-steady state flux of 25 microg cm(-2)h(-1), threefold higher than from a classical emulsion (9.7 microg cm(-2)h(-1)). After 24h exposure, caffeine was mostly in the receptor fluid and in the dermis; cumulated amounts of caffeine were higher for the Pickering emulsion. Several physicochemical phenomena were investigated for clearing up the mechanisms of enhanced permeation from the Pickering emulsion. Among them, higher adhesion of Pickering emulsion droplets to skin surface was disclosed. The transport of caffeine adsorbed on silica particles was also considered relevant since skin stripping showed that aggregates of silica particles entered deeply the stratum corneum.

  11. Mechanism of drug release from an acrylic polymer-wax matrix tablet.

    PubMed

    Huang, H P; Mehta, S C; Radebaugh, G W; Fawzi, M B

    1994-06-01

    An acrylic polymer-wax matrix system was evaluated for oral sustained-release tablets of diphenhydramine HCl. A desirable release profile of diphenhydramine was achieved by incorporating Eudragit L in a carnauba wax matrix. In this polymer-wax system, carnauba wax maintained the integrity of the matrix, whereas Eudragit L slowly eroded in the matrix as the drug was released. Thus, the area-to-volume ratio of the tablet remained constant over the duration of the drug release. In vitro drug release studies were conducted at physiological pHs that exist in the gastrointestinal tract. Drug release rates decreased as the polymer:drug ratio increased from 1:2 to 2:1. The drug release rate was faster in pH 7.5 phosphate buffer than in 0.1 N HCl solution. The drug release from these polymer-wax matrices is described by a combination diffusion/erosion mechanism. Based on the typical pH encountered in intestinal fluids, complete dissolution of the drug and polymer at pH 7.5 in 8-10 h would ensure good bioavailability of the drug following oral administration.

  12. Swelling/floating capability and drug release characterizations of gastroretentive drug delivery system based on a combination of hydroxyethyl cellulose and sodium carboxymethyl cellulose.

    PubMed

    Chen, Ying-Chen; Ho, Hsiu-O; Liu, Der-Zen; Siow, Wen-Shian; Sheu, Ming-Thau

    2015-01-01

    The aim of this study was to characterize the swelling and floating behaviors of gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS to incorporate three model drugs with different solubilities (metformin, ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated, and their swelling and floating behaviors were characterized. Influences of media containing various NaCl concentrations on the swelling and floating behaviors and drug solubility were also characterized. Finally, release profiles of the three model drugs from GRDDS formulation (F1-4) and formulation (F1-1) were examined. Results demonstrated when the GRDDS tablets were tested in simulated gastric solution, the degree of swelling at 6 h was decreased for each formulation that contained NaCMC in comparison to those in de-ionized water (DIW). Of note, floating duration was enhanced when in simulated gastric solution compared to DIW. Further, the hydration of tablets was found to be retarded as the NaCl concentration in the medium increased resulting in smaller gel layers and swelling sizes. Dissolution profiles of the three model drugs in media containing various concentrations of NaCl showed that the addition of NaCl to the media affected the solubility of the drugs, and also their gelling behaviors, resulting in different mechanisms for controlling a drug's release. The release mechanism of the freely water-soluble drug, metformin, was mainly diffusion-controlled, while those of the water-soluble drug, ciprofloxacin, and the slightly water-soluble drug, esomeprazole, were mainly anomalous diffusion. Overall results showed that the developed GRDDS composed of HEC 250HHX and NaCMC of 450 cps possessed proper swelling extents and desired floating periods with sustained-release characteristics.

  13. Thermo-responsive hydrogels with N-isopropylacrylamide/acrylamide interpenetrating networks for controlled drug release.

    PubMed

    Jiang, Yu; Wu, Yanye; Huo, Yinlei

    2015-01-01

    Series of thermo-sensitive hydrogels (PNAs) based on N-isopropylacrylamide/acrylamide interpenetrating polymer networks were synthesized via in situ free-radical polymerization. Poly (ethylene glycol diacrylate) and poly (ε-caprolactone diacrylate) were synthesized as macro-cross-linkers due to their excellent biocompatibilities. The macro-cross-linkers and hydrogels were characterized by (1)H NMR and FT-IR, respectively. The interior morphology of the hydrogels was observed by scanning electron microscopy. The swelling ratios at different temperatures and the swelling/deswelling kinetics of the hydrogels were studied. Their volume phase transition temperatures were also measured by differential scanning calorimetry characterization. The results indicated that the PNA hydrogels had uniform macroporous structures, and they not only had considerable swelling ratios, but also exhibited rapid swelling/deswelling kinetics and response sensitivities. In addition, the weight ratio of AAm/NIPAAm also affected the swelling performance and phase transition temperature of hydrogels, and its value less than 5% was the optimal proportion to achieve excellent comprehensive properties. Levofloxacin lactate and Naproxen were selected as drugs and simulated in vitro condition release, and the drug release results showed that the PNA hydrogels behaved fast release performance.

  14. Quantitative ToF-SIMS studies of protein drug release from biodegradable polymer drug delivery membranes

    NASA Astrophysics Data System (ADS)

    Burns, Sarah A.; Gardella, Joseph A.

    2008-12-01

    Biodegradable polymers are of interest in developing strategies to control protein drug delivery. The protein that was used in this study is Keratinocyte Growth Factor (KGF) which is a protein involved in the re-epithelialization process. The protein is stabilized in the biodegradable polymer matrix during formulation and over the course of polymer degradation with the use of an ionic surfactant Aerosol-OT (AOT) which will encapsulate the protein in an aqueous environment. The release kinetics of the protein from the surface of these materials requires precise timing which is a crucial factor in the efficacy of this drug delivery system. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used in the same capacity to identify the molecular ion peak of the surfactant and polymer and use this to determine surface concentration. In the polymer matrix, the surfactant molecular ion peak was observed in the positive and negative mode at m/ z 467 and 421, respectively. These peaks were determined to be [AOT + Na +] and [AOT - Na +]. These methods are used to identify the surfactant and protein from the polymer matrix and are used to measure the rate of surface accumulation. The second step was to compare this accumulation rate with the release rate of the protein into an aqueous solution during the degradation of the biodegradable film. This rate is compared to that from fluorescence spectroscopy measurements using the protein autofluorescence from that released into aqueous solution [C.M. Mahoney, J. Yu, A. Fahey, J.A.J. Gardella, SIMS depth profiling of polymer blends with protein based drugs, Appl. Surf. Sci. 252 (2006), 6609-6614.].

  15. Drug release from MCC- and carrageenan-based pellets: experiment and theory.

    PubMed

    Kranz, H; Jürgens, K; Pinier, M; Siepmann, J

    2009-10-01

    Microcrystalline cellulose (MCC) is a well-established pelletisation aid. However, MCC pellets generally do not disintegrate, resulting in prolonged drug release, especially in the case of drugs with poor/low aqueous solubility. The major objectives of this study were (i) to modify the prolonged matrix-type drug release from MCC pellets by addition of a disintegrant (croscarmellose Na) or pore former (PEG 6000), (ii) to evaluate carrageenan as potential alternative pelletisation aid for manufacturing high-dose immediate release pellets, and (iii) to better understand the underlying drug release mechanisms. Pellets containing 77-90% drug with poor/low aqueous solubility (vatalanib succinate, SAG/ZK, or theophylline) were prepared by extrusion-spheronisation. All batches showed acceptable yields, aspect ratios, tensile strengths, and porosities. Drug release from MCC pellets was predominantly controlled by pure diffusion and limited drug solubility and could be quantitatively described using Fick's law. Importantly, the apparent drug diffusivity could effectively be adjusted by adding small amounts of a disintegrant or pore former, allowing for release periods ranging from a few minutes to several hours. The drug diffusion coefficients varied between 0.36 and 29 x 10(-6)cm(2)/s. In contrast, carrageenan-based pellets very rapidly disintegrated upon contact with aqueous media and released high doses of drugs with poor/low aqueous solubility within a few minutes.

  16. Simultaneous quantification of drug release and erosion from hypromellose hydrophilic matrices.

    PubMed

    Ghori, Muhammad U; Ginting, Gidion; Smith, Alan M; Conway, Barbara R

    2014-04-25

    Hypromellose, HPMC, is frequently used to control drug release from matrix tablet formulations. Drug is released by a combination of diffusion through and erosion of, the matrix and is usually measured invitro by separate dissolution and swelling/erosion studies. The present study was designed to measure matrix erosion, polymer dissolution and drug release kinetics and their inter-relationship in a single experiment using a phenol-sulphuric acid assay to quantify dissolved HPMC alongside spectrophotometrical analysis of drug release. HPMC-based matrix tablets were manufactured containing two drugs at various drug:HPMC ratios. Drug release was determined and the degree of erosion was calculated by gravimetry. Results showed the matrix erosion rate and drug release were dependent on HPMC content and drug solubility, as expected. It was also apparent that the erosion rate was directly related to the drug release kinetics and comparative analysis of both matrix erosion techniques showed a high level of correlation. The findings show that a simple and inexpensive assay can be utilised not only to quantify HPMC but can also be used to calculate the degree of erosion of tablet matrices, negating the need for a separate study and providing a simplified practical approach that may be of use during product optimization.

  17. Monitoring pH-Triggered Drug Release from Radioluminescent Nanocapsules with X-Ray Excited Optical Luminescence

    PubMed Central

    Chen, Hongyu; Moore, Thomas; Qi, Bin; Colvin, Daniel C.; Jelen, Erika K.; Hitchcock, Dale A.; He, Jian; Mefford, O. Thompson; Gore, John C.; Alexis, Frank; Anker, Jeffrey N.

    2013-01-01

    One of the greatest challenges in cancer therapy is to develop methods to deliver chemotherapy agents to tumor cells while reducing systemic toxicity to non-cancerous cells. A promising approach to localizing drug release is to employ drug-loaded nanoparticles with coatings that release the drugs only in the presence of specific triggers found in the target cells such as pH, enzymes, or light. However, many parameters affect the nanoparticle distribution and drug release rate and it is difficult to quantify drug release in situ. In this work, we show proof of principle for a “smart” radioluminescent nanocapsule with X-ray excited optical luminescence (XEOL) spectrum that changes during release of the optically absorbing chemotherapy drug, doxorubicin. XEOL provides an almost background-free luminescent signal for measuring drug release from particles irradiated by a narrow X-ray beam. We study in vitro pH triggered release rates of doxorubicin from nanocapsules coated with a pH responsive polyelectrolyte multilayer using HPLC and XEOL spectroscopy. The doxorubicin was loaded to over 5 % by weight, and released from the capsule with a time constant in vitro of ~ 36 days at pH 7.4, and 21.4 hr at pH 5.0, respectively. The Gd2O2S:Eu nanocapsules are also paramagnetic at room temperature with similar magnetic susceptibility and similarly good MRI T2 relaxivities to Gd2O3, but the sulfur increases the radioluminescence intensity and shifts the spectrum. Empty nanocapsules did not affect cell viability up to concentrations of at least 250 μ/ml. These empty nanocapsules accumulated in a mouse liver and spleen following tail vein injection, and could be observed in vivo using XEOL. The particles are synthesized with a versatile template synthesis technique which allows for control of particle size and shape. The XEOL analysis technique opens the door to non-invasive quantification of drug release as a function of nanoparticle size, shape, surface chemistry and tissue

  18. Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

    PubMed

    Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

    2016-11-01

    This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

  19. Simultaneous monitoring of the drug release and antitumor effect of a novel drug delivery system-MWCNTs/DOX/TC.

    PubMed

    Dong, Xia; Sun, Zhiting; Wang, Xiaoxiao; Zhu, Dunwan; Liu, Lanxia; Leng, Xigang

    2017-11-01

    Monitoring drug release and therapeutic efficacy is crucial for developing drug delivery systems. Our preliminary study demonstrated that, as compared with pristine multiwalled carbon nanotubes (MWCNTs), transactivator of transcription (TAT)-chitosan functionalized MWCNTs (MWCNTs-TC) were a more promising candidate for drug delivery in cancer therapy. In the present study, a MWCNTs/TC-based drug delivery system was developed for an anticancer drug, doxorubicin (DOX). The drug loading and in vitro release profiles, cellular uptake and cytotoxicity were assessed. More importantly, the in vivo drug release and antitumor effect of MWCNTs/DOX/TC were evaluated by noninvasive fluorescence and bioluminescence imaging. It was demonstrated that MWCNTs/DOX/TC can be efficiently taken up by BEL-7402 hepatoma cells. The release of DOX from MWCNTs/DOX/TC was faster under lower pH condition, which was beneficial for intrcellular drug release. The in vivo release process of DOX and antitumor effect in animal model were monitored simultaneously by noninvasive fluorescence and luminescence imaging, which demonstrated the application potential of MWCNTs/DOX/TC for cancer therapy.

  20. Sodium lauryl sulfate impedes drug release from zinc-crosslinked alginate beads: switching from enteric coating release into biphasic profiles.

    PubMed

    Taha, Mutasem O; Nasser, Wissam; Ardakani, Adel; Alkhatib, Hatim S

    2008-02-28

    The aim of this research is to investigate the effects of sodium lauryl sulfate (SLS) on ionotropically cross-linked alginate beads. Different levels of SLS were mixed with sodium alginate and chlorpheniramine maleate (as loaded model drug). The resulting viscous solutions were dropped onto aqueous solutions of zinc or calcium ions for ionotropic curing. The generated beads were assessed by their drug releasing profiles, infrared and differential scanning colorimetery (DSC) traits. SLS was found to exert profound concentration-dependent impacts on the characteristics of zinc-crosslinked alginate beads such that moderate modifications in the levels of SLS switched drug release from enteric coating-like behavior to a biphasic release modifiable to sustained-release by the addition of minute amounts of xanthan gum. Calcium cross-linking failed to reproduce the same behavior, probably due to the mainly ionic nature of calcium-carboxylate bonds compared to the coordinate character of their zinc-carboxylate counterparts. Apparently, moderate levels of SLS repel water penetration into the beads, and therefore minimize chlorpheniramine release. However, higher SLS levels seem to discourage polymeric cross-linking and therefore allow biphasic drug release.

  1. Rheological characterization and drug release studies of gum exudates of Terminalia catappa Linn.

    PubMed

    Kumar, Sadhis V; Sasmal, Dinakar; Pal, Subodh C

    2008-01-01

    The present study was undertaken to evaluate the gum exudates of Terminalia catappa Linn. (TC gum) as a release retarding excipient in oral controlled drug delivery system. The rheological properties of TC gum were studied and different formulation techniques were used to evaluate the comparative drug release characteristics. The viscosity was found to be dependent on concentration and pH. Temperature up to 60 degrees C did not show significant effect on viscosity. The rheological kinetics evaluated by power law, revealed the shear thinning behavior of the TC gum dispersion in water. Matrix tablets of TC gum were prepared with the model drug dextromethorphan hydrobromide (DH) by direct compression, wet granulation and solid dispersion techniques. The dissolution profiles of the matrix tablets were compared with the pure drug containing capsules using the USP Basket apparatus with 500 ml phosphate buffer of pH 6.8 as a dissolution medium. The drug release from the compressed tablets containing TC gum was comparatively sustained than pure drug containing capsules. Even though all the formulation techniques showed reduction of dissolution rate, aqueous wet granulation showed the maximum sustained release of more than 8 h. The release kinetics estimated by the power law revealed that the drug release mechanism involved in the dextromethorphan matrix is anomalous transport as indicated by the release exponent n values. Thus the study confirmed that the TC gum might be used in the controlled drug delivery system as a release-retarding polymer.

  2. Modulating Drug Release from Gastric-Floating Microcapsules through Spray-Coating Layers

    PubMed Central

    Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

    2014-01-01

    Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system. PMID:25470374

  3. Measure your septa release ratios: pheromone release ratio variability affected by rubber septa and solvent.

    PubMed

    Kuenen, L P S; Siegel, Joel P

    2015-03-01

    The type of solvent and the volume used to load pheromone components onto rubber septa had significant effects on pheromone release ratios, the variability of those release ratios, and the recoverability of the volatile components during subsequent extraction with hexane. Volatile release ratios of synthetic Oriental fruit moth (OFM) pheromone and additional volatile compounds were determined using a gas chromatograph column as a volatile trap for rapid (≤1 hr) analysis from individual rubber septa. Volatile compound solutions were prepared in hexane, pentane, CH2Cl2, and methyl tert-butyl ether, and a 10, 33, or 100 μl aliquot of each solution was applied to rubber septa. Septa loaded with 100 μl of CH2Cl2 emitted significantly (P < 0.05) higher alcohol: acetate (OH:Ac) ratios than septa loaded with the other solvents, which were all similar. Release ratios of the alcohol and acetate components of the OFM pheromone components were assessed over a 3 week period using septa loaded with each solvent. Regardless of loading solvent, the OFM OH:Ac ratios declined logarithmically over 3 weeks; however, the decay slope from septa loaded with CH2Cl2 solutions was different from those of the other three solvents, which were nearly all the same. A high variability in OH:Ac release ratios was measured overall, regardless of the solvent used or the volume it was applied in. Four compounds of near-equal mass: 1-dodecanol, 1-dodecanal, methyl decanoate, and tridecane emitted different release ratios dependent on the solvent, hexane or CH2Cl2, with which a septum was loaded. The more polar and the greater the mass of the test compound, the slower it was emitted from a septum regardless of solvent. These combined results plus comparisons to earlier reports, suggest that researchers should empirically assess the release ratios from septa to be used in bioassays rather than just reporting the type of septum, ratios of compounds applied and solvent used to prepare them.

  4. Modulation of drug release kinetics of shellac-based matrix tablets by in-situ polymerization through annealing process.

    PubMed

    Limmatvapirat, Sontaya; Limmatvapirat, Chutima; Puttipipatkhachorn, Satit; Nunthanid, Jurairat; Luangtana-anan, Manee; Sriamornsak, Pornsak

    2008-08-01

    A new oral-controlled release matrix tablet based on shellac polymer was designed and developed, using metronidazole (MZ) as a model drug. The shellac-based matrix tablets were prepared by wet granulation using different amounts of shellac and lactose. The effect of annealing temperature and pH of medium on drug release from matrix tablets was investigated. The increased amount of shellac and increased annealing temperature significantly affected the physical properties (i.e., tablet hardness and tablet disintegration) and MZ release from the matrix tablets. The in-situ polymerization played a major role on the changes in shellac properties during annealing process. Though the shellac did not dissolve in acid medium, the MZ release in 0.1N HCl was faster than in pH 7.3 buffer, resulting from a higher solubility of MZ in acid medium. The modulation of MZ release kinetics from shellac-based matrix tablets could be accomplished by varying the amount of shellac or annealing temperature. The release kinetics was shifted from relaxation-controlled release to diffusion-controlled release when the amount of shellac or the annealing temperature was increased.

  5. Composite poly(vinyl alcohol)/poly(vinyl acetate) electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs.

    PubMed

    Jannesari, Marziyeh; Varshosaz, Jaleh; Morshed, Mohammad; Zamani, Maedeh

    2011-01-01

    The aim of this study was to develop novel biomedicated nanofiber electrospun mats for controlled drug release, especially drug release directly to an injury site to accelerate wound healing. Nanofibers of poly(vinyl alcohol) (PVA), poly(vinyl acetate) (PVAc), and a 50:50 composite blend, loaded with ciprofloxacin HCl (CipHCl), were successfully prepared by an electrospinning technique for the first time. The morphology and average diameter of the electrospun nanofibers were investigated by scanning electron microscopy. X-ray diffraction studies indicated an amorphous distribution of the drug inside the nanofiber blend. Introducing the drug into polymeric solutions significantly decreased solution viscosities as well as nanofiber diameter. In vitro drug release evaluations showed that both the kind of polymer and the amount of drug loaded greatly affected the degree of swelling, weight loss, and initial burst and rate of drug release. Blending PVA and PVAc exhibited a useful and convenient method for electrospinning in order to control the rate and period of drug release in wound healing applications. Also, the thickness of the blend nanofiber mats strongly influenced the initial release and rate of drug release.

  6. 3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics.

    PubMed

    Goyanes, Alvaro; Wang, Jie; Buanz, Asma; Martínez-Pacheco, Ramón; Telford, Richard; Gaisford, Simon; Basit, Abdul W

    2015-11-02

    Three dimensional printing (3D printing) was used to fabricate novel oral drug delivery devices with specialized design configurations. Each device was loaded with multiple actives, with the intent of applying this process to the production of personalized medicines tailored at the point of dispensing or use. A filament extruder was used to obtain drug-loaded--paracetamol (acetaminophen) or caffeine--filaments of poly(vinyl alcohol) with characteristics suitable for use in fused-deposition modeling 3D printing. A multinozzle 3D printer enabled fabrication of capsule-shaped solid devices containing the drug with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different to the drug in the adjacent layers, and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least-squares component matching to produce false color representations of distribution of the drugs was used. This clearly showed a definitive separation between the drug layers of paracetamol and caffeine. Drug release tests in biorelevant bicarbonate media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both paracetamol and caffeine was simultaneous and independent of drug solubility. With the DuoCaplet design, it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device; the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design

  7. Swelling/Floating Capability and Drug Release Characterizations of Gastroretentive Drug Delivery System Based on a Combination of Hydroxyethyl Cellulose and Sodium Carboxymethyl Cellulose

    PubMed Central

    Chen, Ying-Chen; Ho, Hsiu-O; Liu, Der-Zen; Siow, Wen-Shian; Sheu, Ming-Thau

    2015-01-01

    The aim of this study was to characterize the swelling and floating behaviors of gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS to incorporate three model drugs with different solubilities (metformin, ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated, and their swelling and floating behaviors were characterized. Influences of media containing various NaCl concentrations on the swelling and floating behaviors and drug solubility were also characterized. Finally, release profiles of the three model drugs from GRDDS formulation (F1-4) and formulation (F1-1) were examined. Results demonstrated when the GRDDS tablets were tested in simulated gastric solution, the degree of swelling at 6 h was decreased for each formulation that contained NaCMC in comparison to those in de-ionized water (DIW). Of note, floating duration was enhanced when in simulated gastric solution compared to DIW. Further, the hydration of tablets was found to be retarded as the NaCl concentration in the medium increased resulting in smaller gel layers and swelling sizes. Dissolution profiles of the three model drugs in media containing various concentrations of NaCl showed that the addition of NaCl to the media affected the solubility of the drugs, and also their gelling behaviors, resulting in different mechanisms for controlling a drug’s release. The release mechanism of the freely water-soluble drug, metformin, was mainly diffusion-controlled, while those of the water-soluble drug, ciprofloxacin, and the slightly water-soluble drug, esomeprazole, were mainly anomalous diffusion. Overall results showed that the developed GRDDS composed of HEC 250HHX and NaCMC of 450 cps possessed proper swelling extents and desired floating periods with sustained-release characteristics. PMID:25617891

  8. Synthesis characterization and in vitro drug release from acrylamide and sodium alginate based superporous hydrogel devices

    PubMed Central

    Nagpal, Manju; Singh, Shailendra Kumar; Mishra, Dinanath

    2013-01-01

    Objective: Present investigation was aimed at developing gastroretentive superporous hydrogels (SPHs) having desired mechanical characteristics with sustained release. Materials and Methods: The acrylamide based SPHs of various generations (1st, 2nd and 3rd) were synthesized by gas blowing technique. The prepared SPHs were evaluated for swelling, mechanical strength studies and scanning electron microscopy studies. Verapamil hydrochloride was loaded into selected SPHs by aqueous drug loading method and characterized via Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (X-RD), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR) and in vitro drug release studies. Results: SPHs of third generation were observed to have desired mechanical strength with sufficient swelling properties. Integrity of the drug was maintained in hydrogel polymeric network as indicated by FTIR, X-RD, and DSC and NMR studies. Initially, fast drug release (up to 60%) was observed in 30 min in formulation batches containing pure drug only (A, C and E), which was further sustained untill 24 h. Discussion: The increase in mechanical strength was due to the chemical cross-linking of secondary polymer in hydrogel network. The initial burst release was due to the presence of free drug at the surface and later sustained drug release was due to diffusion of entrapped drug in polymeric network. Significant decrease in drug release was observed by the addition of hydroxypropyl methyl cellulose. Conclusion: SPH interpenetrating networks with fast swelling and sufficient mechanical strength were prepared, which can be potentially exploited for designing gastroretentive drug delivery devices. PMID:24167785

  9. Use of anodized titanium alloy as drug carrier: Ibuprofen as model of drug releasing.

    PubMed

    Doadrio, Antonio L; Conde, A; Arenas, M A; Hernández-López, J M; de Damborenea, J J; Pérez-Jorge, Concepción; Esteban, Jaime; Vallet-Regí, Maria

    2015-08-15

    The use of osteoarticular implants has improved the quality of life of millions of patients. In this work nanotubular structures tailored made on Ti6Al4V substrates was used as drug delivery system of ibuprofen as a proof of concept. Three different nanotubular films with different sizes and forms (NT, NT+ and NTb) were analysed. Samples were soaked in a solution of 660 mg ibuprofen/20 mL n-pentane. The ibuprofen release in aqueous medium was evaluated by liquid chromatography reversed-phase (RP-HPLC). To calculate the observed constant k, the amount of ibuprofen released was plotted versus the time using linear regression according to the zero-order, first-order, second-order and Higuchi model. The release of ibuprofen was constant and independent of the concentration. The kinetic constant obtained was 0.021 (NT), 0.022 (NT+) and 0.013 (NTb) being the correlation factor of 0.98 (zero-order) where the maximum correlation factor was reached. These results indicate that the delivery process from NT and NT+ is similar and slower that NTb. In all the cases was inside the therapeutically range. These results showed the potential of these modifications in order to develop implants that can carry different molecules of medical importance.

  10. Control of drug release from capsules using high frequency energy transmission systems.

    PubMed

    Gröning, R; Bensmann, H; Müller, R S

    2008-11-19

    In the present investigations new drug delivery systems have been developed, which are controlled by a computer and a high frequency energy transmission system. The capsules consist of a drug reservoir, a high frequency receiver, a gas generating section and a piston to pump a drug solution or drug suspension out of the reservoir. Mechanical energy is generated inside the capsule through electrolysis, if a 27 MHz high frequency field is in resonance with the receiver inside the capsule. Two different miniaturised oscillatory circuits were constructed, which act as the receivers in the capsules. Tramadol was used in release experiments as a model drug. Delayed and pulsed release profiles were obtained. A computer-controlled system was constructed, in which the programmed release profiles are compared with the actual release of the drug.

  11. Drug release from nanoparticles embedded in four different nanofibrillar cellulose aerogels.

    PubMed

    Valo, Hanna; Arola, Suvi; Laaksonen, Päivi; Torkkeli, Mika; Peltonen, Leena; Linder, Markus B; Serimaa, Ritva; Kuga, Shigenori; Hirvonen, Jouni; Laaksonen, Timo

    2013-09-27

    Highly porous nanocellulose aerogels prepared by freeze-drying from various nanofibrillar cellulose (NFC) hydrogels are introduced as nanoparticle reservoirs for oral drug delivery systems. Here we show that beclomethasone dipropionate (BDP) nanoparticles coated with amphiphilic hydrophobin proteins can be well integrated into the NFC aerogels. NFCs from four different origins are introduced and compared to microcrystalline cellulose (MCC). The nanocellulose aerogel scaffolds made from red pepper (RC) and MCC release the drug immediately, while bacterial cellulose (BC), quince seed (QC) and TEMPO-oxidized birch cellulose-based (TC) aerogels show sustained drug release. Since the release of the drug is controlled by the structure and interactions between the nanoparticles and the cellulose matrix, modulation of the matrix formers enable a control of the drug release rate. These nanocomposite structures can be very useful in many pharmaceutical nanoparticle applications and open up new possibilities as carriers for controlled drug delivery.

  12. Ingenious pH-sensitive dextran/mesoporous silica nanoparticles based drug delivery systems for controlled intracellular drug release.

    PubMed

    Zhang, Min; Liu, Jia; Kuang, Ying; Li, Qilin; Zheng, Di-Wei; Song, Qiongfang; Chen, Hui; Chen, Xueqin; Xu, Yanglin; Li, Cao; Jiang, Bingbing

    2017-02-04

    In this work, dextran, a polysaccharide with excellent biocompatibility, is applied as the "gatekeeper" to fabricate the pH-sensitive dextran/mesoporous silica nanoparticles (MSNs) based drug delivery systems for controlled intracellular drug release. Dextran encapsulating on the surface of MSNs is oxidized by NaIO4 to obtain three kinds of dextran dialdehydes (PADs), which are then coupled with MSNs via pH-sensitive hydrazone bond to fabricate three kinds of drug carriers. At pH 7.4, PADs block the pores to prevent premature release of anti-cancer drug doxorubicin hydrochloride (DOX). However, in the weakly acidic intracellular environment (pH∼5.5) the hydrazone can be ruptured; and the drug can be released from the carriers. The drug loading capacity, entrapment efficiency and release rates of the drug carriers can be adjusted by the amount of NaIO4 applied in the oxidation reaction. And from which DOX@MSN-NH-N=C-PAD10 is chosen as the most satisfactory one for the further in vitro cytotoxicity studies and cellular uptake studies. The results demonstrate that DOX@MSN-NH-N=C-PAD10 with an excellent pH-sensitivity can enter HeLa cells to release DOX intracellular due to the weakly acidic pH intracellular and kill the cells. In our opinion, the ingenious pH-sensitive drug delivery systems have application potentials for cancer therapy.

  13. Iron Deprivation Affects Drug Susceptibilities of Mycobacteria Targeting Membrane Integrity

    PubMed Central

    Pal, Rahul; Hameed, Saif; Fatima, Zeeshan

    2015-01-01

    Multidrug resistance (MDR) acquired by Mycobacterium tuberculosis (MTB) through continuous deployment of antitubercular drugs warrants immediate search for novel targets and mechanisms. The ability of MTB to sense and become accustomed to changes in the host is essential for survival and confers the basis of infection. A crucial condition that MTB must surmount is iron limitation, during the establishment of infection, since iron is required by both bacteria and humans. This study focuses on how iron deprivation affects drug susceptibilities of known anti-TB drugs in Mycobacterium smegmatis, a “surrogate of MTB.” We showed that iron deprivation leads to enhanced potency of most commonly used first line anti-TB drugs that could be reverted upon iron supplementation. We explored that membrane homeostasis is disrupted upon iron deprivation as revealed by enhanced membrane permeability and hypersensitivity to membrane perturbing agent leading to increased passive diffusion of drug and TEM images showing detectable differences in cell envelope thickness. Furthermore, iron seems to be indispensable to sustain genotoxic stress suggesting its possible role in DNA repair machinery. Taken together, we for the first time established a link between cellular iron and drug susceptibility of mycobacteria suggesting iron as novel determinant to combat MDR. PMID:26779346

  14. Drug delivery through the sclera: effects of thickness, hydration, and sustained release systems.

    PubMed

    Lee, Sang-Bumm; Geroski, Dayle H; Prausnitz, Mark R; Edelhauser, Henry F

    2004-03-01

    The purpose of this study was to determine whether trans-scleral pressure affects scleral solute permeability by altering scleral thickness or hydration, and to investigate the sustained release delivery of dexamethasone. Scleral sections from donor human globes were mounted for in vitro flux studies. Scleral thickness and hydration were measured as functions of trans-scleral pressure. For the sustained release studies, 3H-dexamethasone in pluronic F-127 gel or in fibrin sealant was added to the episcleral side of the tissue and flux studies were performed. While scleral thickness showed a tendency to decrease with increasing pressure, a significant decrease in thickness was measured only at a trans-scleral pressure of 60 mmHg. No significant changes in scleral hydration were measured over the range of trans-scleral pressures studied. The apparent permeability constants (Ktrans) of human sclera for 3H-dexamethasone in BSS plus, fibrin sealant and F-127 gel were 11.5 x 10(-6), 7.3 x 10(-6), and 1.5 x 10(-6) cm sec(-1), respectively. Human scleral permeability to dexamethasone differed significantly among the three vehicles (p < 0.0001). Cumulative delivery of dexamethasone from BSS plus, F-127 gel, and fibrin sealant were 85.0, 29.3, and 67.9% at 20 hr, respectively. Scleral hydration was unaffected by trans-scleral pressures. Scleral thinning was only observed at 60 mmHg. Trans-scleral pressures below 60 mmHg would not be expected to significantly affect the permeability of the tissue to solutes in the size range of conventional drugs. F-127 gel and fibrin sealant provided a slow, relatively uniform sustained release through a 24 hr period. These systems might be employed to achieve sustained therapeutic levels of drugs to the posterior segment of eye.

  15. Chitosan-polycarbophil complexes in swellable matrix systems for controlled drug release.

    PubMed

    Lu, Z; Chen, W; Hamman, J H

    2007-10-01

    A prerequisite for progress in the design of novel drug delivery systems is the development of excipients that are capable of fulfilling multifunctional roles such as controlling the release of the drug according to the therapeutic needs. Although several polymers have been utilised in the development of specialised drug delivery systems, their scope in dosage form design can be enlarged through combining different polymers. When a polymer is cross-linked or complexed with an oppositely charged polyelectrolyte, a three-dimensional network is formed in which the drug can be incorporated to control its release. The swelling properties and release kinetics of two model drugs with different water solubilities (i.e. diltiazem and ibuprofen) from monolithic matrix tablets consisting of an interpolyelectrolyte complex between chitosan and polycarbophil are reported. Matrix tablets consisting of this polymeric complex without drug or excipients exhibited extremely high swelling properties that are completely reversible upon drying. The drug release from matrix systems with different formulations depended on the concentration of the chitosan-polycarbophil interpolyelectrolyte complex and approached zero order release kinetics for both model drugs. The chitosan-polycarbophil interpolyelectrolyte complex has demonstrated a high potential as an excipient for the production of swellable matrix systems with controlled drug release properties.

  16. Time-programmed dual release formulation by multilayered drug-loaded nanofiber meshes.

    PubMed

    Okuda, Tatsuya; Tominaga, Kengo; Kidoaki, Satoru

    2010-04-19

    To develop a drug carrier that enables time-programmed dual release in a single formulation, multilayered drug-loaded biodegradable nanofiber meshes were designed using sequential electrospinning with the following construction: (i) first drug-loaded mesh (top), (ii) barrier mesh, (iii) second drug-loaded mesh, and (iv) basement mesh (bottom). The drug release speed and duration were controlled by designing morphological features of the electrospun meshes such as the fiber diameter and mesh thickness. Control of the timed release of the second drug-the retardation period-was accomplished by appropriate design of the barrier mesh thickness. An in vitro release experiment demonstrated that the tetra-layered construction described above with appropriate morphological features of each component mesh can provide timed dual release of the respective drugs. The time-programmed dual release system using the multilayered electrospun nanofiber meshes was demonstrated as a useful formulation for advanced multidrug combination therapy requiring regiospecific administration of different drugs at different times. The potential use of the present multilayered formulation is discussed for application to biochemical modulation as one administrative strategy for use in sequential chemotherapy employing multiple anti-tumor drugs.

  17. Evaluation of Factors Affecting Powdered Drug Reconstitution in Microgravity

    NASA Technical Reports Server (NTRS)

    Schaffner, Grant; Johnston, Smith; Marshburn, Tom

    1999-01-01

    standard pharmacological supplies. The experiment included a parametric assessment of possible factors affecting the reconstitution process. The specific questions that we wished to answer were: (1) Is it possible to reconstitute powdered drugs in weightlessness using standard pharmacological equipment? (2) What are the differences between drug reconstitution in a 1-G and a 0-G environment? (3) What techniques of mixing the drug powder and diluent are more successful? (4) What physical and chemical factors play a role in determining the success of mixing and dissolution? (5) Is it necessary to employ crewmember and equipment restraints during the reconstitution process?

  18. Effect of ingested lipids on drug dissolution and release with concurrent digestion: a modeling approach

    PubMed Central

    Buyukozturk, Fulden; Di Maio, Selena; Budil, David E.; Carrier, Rebecca L.

    2014-01-01

    Purpose To mechanistically study and model the effect of lipids, either from food or self-emulsifying drug delivery systems (SEDDS), on drug transport in the intestinal lumen. Methods Simultaneous lipid digestion, dissolution/release, and drug partitioning were experimentally studied and modeled for two dosing scenarios: solid drug with a food-associated lipid (soybean oil) and drug solubilized in a model SEDDS (soybean oil and Tween 80 at 1:1 ratio). Rate constants for digestion, permeability of emulsion droplets, and partition coefficients in micellar and oil phases were measured, and used to numerically solve the developed model. Results Strong influence of lipid digestion on drug release from SEDDS and solid drug dissolution into food-associated lipid emulsion were observed and predicted by the developed model. 90 minutes after introduction of SEDDS, there was 9% and 70% drug release in the absence and presence of digestion, respectively. However, overall drug dissolution in the presence of food-associated lipids occurred over a longer period than without digestion. Conclusion A systems-based mechanistic model incorporating simultaneous dynamic processes occurring upon dosing of drug with lipids enabled prediction of aqueous drug concentration profile. This model, once incorporated with a pharmacokinetic model considering processes of drug absorption and drug lymphatic transport in the presence of lipids, could be highly useful for quantitative prediction of impact of lipids on bioavailability of drugs. PMID:24234918

  19. Modeling drug release from hot-melt extruded mini-matrices with constant and non-constant diffusivities.

    PubMed

    Verhoeven, E; Siepmann, F; De Beer, T R M; Van Loo, D; Van den Mooter, G; Remon, J P; Siepmann, J; Vervaet, C

    2009-10-01

    Different types of ethylcellulose-based mini-matrices were prepared by hot-melt extrusion and thoroughly characterized in vitro. Metoprolol tartrate was used as model drug, and various amounts and types of polyethylene glycol (PEG)/polyethylene oxide (PEO) were added as release rate modifiers. Based on the experimental results, appropriate mathematical theories were identified/developed, allowing for a better understanding of the underlying drug release mechanisms. For instance, it could be shown that at high initial PEG/PEO contents and/or intermediate initial PEG/PEO contents of low molecular weight, drug diffusion with time- and position-independent diffusivities is predominant. In contrast, at low initial PEG/PEO contents and intermediate initial PEG/PEO contents of high molecular weight, the time- and position-dependent dynamic changes in the matrix porosities significantly affect the conditions for drug and PEG/PEO diffusion. These dynamic changes must be taken into account in the mathematical model. Importantly, the proposed theories are mechanistic realistic and also allow for the quantitative prediction of the effects of the device design on the resulting drug release patterns. Interestingly, these quantitative predictions could be confirmed by independent experiments. Furthermore, Raman spectroscopy allowed for the determination of the resulting drug concentration-position profiles within the mini-matrices as a function of time and confirmed the theoretical predictions.

  20. Preparation of TiO2 nanotubes/mesoporous calcium silicate composites with controllable drug release.

    PubMed

    Xie, Chunling; Li, Ping; Liu, Yan; Luo, Fei; Xiao, Xiufeng

    2016-10-01

    Nanotube structures such as TiO2 nanotube (TNT) arrays produced by self-ordering electrochemical anodization have been extensively explored for drug delivery applications. In this study, we presented a new implantable drug delivery system that combined mesoporous calcium silicate coating with nanotube structures to achieve a controllable drug release of water soluble and antiphlogistic drug loxoprofen sodium. The results showed that the TiO2 nanotubes/mesoporous calcium silicate composites were successfully fabricated by a simple template method and the deposition of mesoporous calcium silicate increased with the soaking time. Moreover, the rate of deposition of biological mesoporous calcium silicate on amorphous TNTs was better than that on anatase TNTs. Further, zinc-incorporated mesoporous calcium silicate coating, produced by adding a certain concentration of zinc nitrate into the soaking system, displayed improved chemical stability. A significant improvement in the drug release characteristics with reduced burst release and sustained release was demonstrated.

  1. Multimodal imaging of sustained drug release from 3-D poly(propylene fumarate) (PPF) scaffolds.

    PubMed

    Choi, Jonghoon; Kim, Kyobum; Kim, Taeho; Liu, Guanshu; Bar-Shir, Amnon; Hyeon, Taeghwan; McMahon, Michael T; Bulte, Jeff W M; Fisher, John P; Gilad, Assaf A

    2011-12-10

    The potential of poly(propylene fumarate) (PPF) scaffolds as drug carriers was investigated and the kinetics of the drug release quantified using magnetic resonance imaging (MRI) and optical imaging. Three different MR contrast agents were used for coating PPF scaffolds. Initially, iron oxide (IONP) or manganese oxide nanoparticles (MONP) carrying the anti-cancer drug doxorubicin were absorbed or mixed with the scaffold and their release into solution at physiological conditions was measured with MRI and optical imaging. A slow (hours to days) and functional release of the drug molecules into the surrounding solution was observed. In order to examine the release properties of proteins and polypeptides, protamine sulfate, a chemical exchange saturation transfer (CEST) MR contrast agent, was attached to the scaffold. Protamine sulfate showed a steady release rate for the first 24h. Due to its biocompatibility, versatile drug-loading capability and constant release rate, the porous PPF scaffold has potential in various biomedical applications, including MR-guided implantation of drug-dispensing materials, development of drug carrying vehicles, and drug delivery for tumor treatment.

  2. Porous scaffolds of gelatin-hydroxyapatite nanocomposites obtained by biomimetic approach: characterization and antibiotic drug release.

    PubMed

    Kim, Hae-Won; Knowles, Jonathan C; Kim, Hyoun-Ee

    2005-08-01

    Gelatin-hydroxyapatite (HA) nanocomposite porous scaffolds were fabricated biomimetically, and their feasibility as a drug-delivery carrier for tissue-regeneration and wound-healing treatments was addressed. The composite sols were prepared by the precipitation of HA up to 30 wt % within a gelatin solution with the use of calcium and phosphate precursors, and the porous scaffold was obtained by casting the sols and further freeze drying. The obtained bodies were crosslinked with carbodiimide derivatives to retain chemical and thermal integrity. The apatite precipitates were observed to be a poorly crystallized carbonate-substituted HA. The nanocomposite scaffolds had porosities of approximately 89-92% and exhibited a bimodal pore distribution, that is, the macropores (approximately 300-500 microm) of the framework structure, and micropores (approximately 0.5-1 microm) formed on the framework surface. Transmission electron microscopy (TEM) observation revealed the precipitation of highly elongated HA nanocrystals on the gelatin network. The well-developed porous structure and organized nanocomposite configurations were in marked contrast to the directly mixed gelatin-HA powder conventional composites. For drug-release tests, tetracycline, an antibiotic drug, was entrapped within the scaffold, and the drug-release profile was examined with processing parameters, such as HA amount in gelatin, crosslinking degree, and initial drug addition. The drug entrapment decreased with increasing HA amount, but increased with increasing crosslinking degree and initial drug addition. The crosslinking of the gelatin was the prerequisite to sustaining and controlling the drug releases. Compared to pure gelatin, the gelatin-HA nanocomposites had lower drug releases, because of their lower water uptake and degradation. All the nanocomposite scaffolds released drugs in proportion to the initial drug addition, suggesting their capacity to deliver drugs in a controlled manner. Based on

  3. Pair correlation microscopy reveals the role of nanoparticle shape in intracellular transport and site of drug release

    NASA Astrophysics Data System (ADS)

    Hinde, Elizabeth; Thammasiraphop, Kitiphume; Duong, Hien T. T.; Yeow, Jonathan; Karagoz, Bunyamin; Boyer, Cyrille; Gooding, J. Justin; Gaus, Katharina

    2017-01-01

    Nanoparticle size, surface charge and material composition are known to affect the uptake of nanoparticles by cells. However, whether nanoparticle shape affects transport across various barriers inside the cell remains unclear. Here we used pair correlation microscopy to show that polymeric nanoparticles with different shapes but identical surface chemistries moved across the various cellular barriers at different rates, ultimately defining the site of drug release. We measured how micelles, vesicles, rods and worms entered the cell and whether they escaped from the endosomal system and had access to the nucleus via the nuclear pore complex. Rods and worms, but not micelles and vesicles, entered the nucleus by passive diffusion. Improving nuclear access, for example with a nuclear localization signal, resulted in more doxorubicin release inside the nucleus and correlated with greater cytotoxicity. Our results therefore demonstrate that drug delivery across the major cellular barrier, the nuclear envelope, is important for doxorubicin efficiency and can be achieved with appropriately shaped nanoparticles.

  4. Natural melanin: a potential pH-responsive drug release device.

    PubMed

    Araújo, Marco; Viveiros, Raquel; Correia, Tiago R; Correia, Ilídio J; Bonifácio, Vasco D B; Casimiro, Teresa; Aguiar-Ricardo, Ana

    2014-07-20

    This work proposes melanin as a new nanocarrier for pH-responsive drug release. Melanin is an abundant natural polymer that can be easily extracted from cuttlefish as nanoparticles with a suitable size range for drug delivery. However, despite its high potentiality, the application of this biopolymer in the pharmaceutical and biomedical fields is yet to be explored. Herein, melanin nanoparticles were impregnated with metronidazole, chosen as model antibiotic drug, using supercritical carbon dioxide. The drug release profile was investigated at acidic and physiologic pH, and the dominant mechanism was found to follow a non-Fickian transport. Drug release from melanin shows a strong pH dependency, which allied to its biocompatibility and lack of cytotoxicity envisages its potential application as nanocarrier in formulations for colon and intestine targeted drug delivery.

  5. Factors affecting ferulic acid release from Brewer's spent grain by Fusarium oxysporum enzymatic system.

    PubMed

    Xiros, Charilaos; Moukouli, Maria; Topakas, Evangelos; Christakopoulos, Paul

    2009-12-01

    In this study, the factors affecting ferulic acid (FA) release from Brewer's spent grain (BSG), by the crude enzyme extract of Fusarium oxysporum were investigated. In order to evaluate the importance of the multienzyme preparation on FA release, the synergistic action of feruloyl esterase (FAE, FoFaeC-12213) and xylanase (Trichoderma longibrachiatum M3) monoenzymes was studied. More than double amount of FA release (1 mg g(-1) dry BSG) was observed during hydrolytic reactions by the crude enzyme extract compared to hydrolysis by the monoenzymes (0.37 mg g(-1) dry BSG). The protease content of the crude extract and the inhibitory effect of FA as an end-product were also evaluated concerning their effect on FA release. The protease treatment prior to hydrolysis by monoenzymes enhanced FA release about 100%, while, for the first time in literature, FA in solution found to have a significant inhibitory effect on FAE activity and on total FA release.

  6. Factors affecting the development of adverse drug reactions (Review article)

    PubMed Central

    Alomar, Muaed Jamal

    2013-01-01

    Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818

  7. Experiment on formulation and drug release behavior of porosity asymmetric membrane capsules in vitro.

    PubMed

    Fu, Hong-Xing; Li, Hui; Zhang, Fu-Zhi; Zhao, Ying-Zheng; Wan, Chang-Wei; Chen, Mi-Te; Jia, Xue-Chao; Yan, Li; Sun, Chuan-Chuan; Xu, Yan-Yan

    2012-06-01

    Porosity asymmetric membrane capsules were prepared to study the relationship between the capsule formulation and drug release. Cellulose acetate (CA) and pore formers were used in the capsule shell formulation as the main semipermeable membrane material. The capsules were permeable to both water and dissolved solutes. Using sparingly soluble drug acetaminophen as a model, cumulative release was calculated. The slope of the release profile from the distilled water had good relationship with the concentration of the pore formers F68. The release of acetaminophen was independent to the pH, osmotic pressure of dissolution medium, but influenced by intensity of agitation. When the concentration of pore former was low, zero-order release behavior was observed within 24 h which was consistent with Fickian diffusion model. When the concentration of pore former was high, however, Higuchi model release was found which is caused by Fickian diffusion and osmotic pressure release. With scanning electron microscope (SEM), the surface structure and cross-section of the capsule shell were also studied before and after drug delivery. With simple preparation and broad scope of drug application, porosity asymmetric membrane capsules can give desired drug extended release and show more convenience than controlled tablets with laser drilling.

  8. Fused-filament 3D printing of drug products: Microstructure analysis and drug release characteristics of PVA-based caplets.

    PubMed

    Goyanes, Alvaro; Kobayashi, Masanori; Martínez-Pacheco, Ramón; Gaisford, Simon; Basit, Abdul W

    2016-11-30

    Fused deposition modeling (FDM) 3-Dimensional (3D) printing is becoming an increasingly important technology in the pharmaceutical sciences, since it allows the manufacture of personalized oral dosage forms by deposition of thin layers of material. Here, a filament extruder was used to obtain filaments of polyvinyl alcohol (PVA) containing paracetamol or caffeine appropriate for 3D printing. The filaments were used to manufacture caplets for oral administration by FDM 3D printing, with the aim of evaluating the effect of the internal structure (micropore volume), drug loading and composition on drug dissolution behaviour. Micropore volume of the caplets was primarily determined by the presence of large pores due to gaps in the printed layers/net while printing, and the porosity of the caplets was 10 fold higher than the porosity of the extruded filament. Dynamic dissolution drug release tests on the caplets in biorelevant bicarbonate media revealed distinctive release profiles, which were dependent on drug solubility and drug loading. Porosity of the caplets did not help to predict the different drug release profiles. This study confirms the potential of 3D printing to fabricate caplets and helps to elucidate which factors influence drug release from this type of new dosage form.

  9. Polyelectrolyte Complex Based Interfacial Drug Delivery System with Controlled Loading and Improved Release Performance for Bone Therapeutics

    PubMed Central

    Vehlow, David; Schmidt, Romy; Gebert, Annett; Siebert, Maximilian; Lips, Katrin Susanne; Müller, Martin

    2016-01-01

    An improved interfacial drug delivery system (DDS) based on polyelectrolyte complex (PEC) coatings with controlled drug loading and improved release performance was elaborated. The cationic homopolypeptide poly(l-lysine) (PLL) was complexed with a mixture of two cellulose sulfates (CS) of low and high degree of substitution, so that the CS and PLL solution have around equal molar charged units. As drugs the antibiotic rifampicin (RIF) and the bisphosphonate risedronate (RIS) were integrated. As an important advantage over previous PEC systems this one can be centrifuged, the supernatant discarded, the dense pellet phase (coacervate) separated, and again redispersed in fresh water phase. This behavior has three benefits: (i) Access to the loading capacity of the drug, since the concentration of the free drug can be measured by spectroscopy; (ii) lower initial burst and higher residual amount of drug due to removal of unbound drug and (iii) complete adhesive stability due to the removal of polyelectrolytes (PEL) excess component. It was found that the pH value and ionic strength strongly affected drug content and release of RIS and RIF. At the clinically relevant implant material (Ti40Nb) similar PEC adhesive and drug release properties compared to the model substrate were found. Unloaded PEC coatings at Ti40Nb showed a similar number and morphology of above cultivated human mesenchymal stem cells (hMSC) compared to uncoated Ti40Nb and resulted in considerable production of bone mineral. RIS loaded PEC coatings showed similar effects after 24 h but resulted in reduced number and unhealthy appearance of hMSC after 48 h due to cell toxicity of RIS.

  10. Co-extrusion as manufacturing technique for multilayer mini-matrices with dual drug release.

    PubMed

    Dierickx, L; Remon, J P; Vervaet, C

    2013-11-01

    The aim of this work was to develop by means of co-extrusion a multilayered dosage form characterized by a dual release profile of the same drug. Co-extrudates consisted of two concentric polymer matrices: a core having a lipophilic character and a coat with a hydrophilic character. Diclofenac sodium (DS) was incorporated as model drug in both layers. Several polymers were screened on the basis of their processability via hot melt extrusion (HME) and in vitro drug release. Polymer combinations with suitable properties (i.e., similar extrusion temperature, appropriate drug release profile) were processed via co-extrusion. (Co-) extruded samples were characterized in terms of solid state (XRD, SEM), in vitro drug release, core/coat adhesion, and bioavailability. Based on the polymer screening, two polymer combinations were selected for co-extrusion: ethylcellulose (core) combined with Soluplus® (coat) and polycaprolactone (core) with PEO (coat). These combinations were successfully co-extruded. XRD revealed that DS remained crystalline during extrusion in ethylcellulose, Soluplus®, polycaprolactone, and PEO. The polycaprolactone/PEO combination could be processed at a lower temperature (70 °C), vs. 140 °C for ethylcellulose/Soluplus®. The maximum drug load in core and coat depended on the extrusion temperature and the die dimensions, while adhesion between core and coat was mainly determined by the drug load and by the extrusion temperature. In vitro drug release from the co-extruded formulations was reflected in the in vivo behavior: formulations with a higher DS content in the coat (i.e., faster drug release) resulted in higher Cmax and higher AUC values. Co-extrusion is a viable method to produce in a single step a multilayer dosage form with dual drug release.

  11. Drug Release from Inert Spherical Matrix Systems Using Monte Carlo Simulations.

    PubMed

    Villalobos, Rafael; Garcia, Erika V; Quintanar, David; Young, Paul M

    2016-05-12

    The objective of this research is to study the behavior of drug delivery from inert spherical matrix systems of different size by means of computer simulation. To simulate the matrix medium, a simple cubic lattice was used, which was sectioned to make a spherical macroscopic system. The sites within the system were randomly occupied by drug-particles or excipient-particles in accordance with chosen drug/excipient ratios. Then, the drug was released from the matrix system simulating a diffusion process. It was found that the release from these systems over short time scales is properly described by the power equation. When the released fraction was processed until 90% release, the Weibull equation suitably expressed the release profiles. On the basis of the analysis of the previous model equations, it was found that close to the percolation threshold an anomalous released occurs, while in the systems with an initial drug load greater than 0.45, the released was Fickian type. Through computer simulation, it was also possible to determine the amount of drug trapped in the matrix, which was found to be a function of the initial drug load. The relationship between the two mentioned variables was adequately described by a model that involves the error function. Based on the results obtained from the amount of drug trapped according to initial drug load and by means of a non-linear regression to the previous model, it was possible to determine the drug percolation threshold in these matrix devices. It was found that the percolation threshold is consistent with the value predicted by the percolation theory.

  12. Correlation between digestion of the lipid phase of smedds and release of the anti-HIV drug UC 781 and the anti-mycotic drug enilconazole from smedds.

    PubMed

    Goddeeris, C; Coacci, J; Van den Mooter, G

    2007-05-01

    The present studies were conducted primarily to compare the drug release process of the anti-HIV drug UC781 from three different smedds to the smedds digestion profile. The influence of every formulation component on the digestion process, measured as the release of fatty acids, was determined. In addition, the release of the antimycotic drug enilconazole from a smedds was investigated as well in order to study the influence of the type of incorporated drug on oil digestion. Simulsol 1292, Tween 80, Cremophor RH40, ethanol and both drugs reduced the fatty acid release. C8, C10 and C12 fatty acids, originating from oil hydrolysis, were able to reverse the inhibitory effect of phospholipids present in the release medium. Similarly Cremophor RH40 lost its inhibitory capacities in combination with Captex 200P hydrolysis. In addition, UC781 did not decrease fatty acid release in combination with a Captex 200P-Tween 80-ethanol mixture. The release of UC781 from smedds significantly increased compared to the dissolution of the pure drug. The drug release profiles were characterized by rapid and complete release followed by precipitation. In order to detect possible correlations between drug release and oil digestion, release results were compared to those of vehicle digestion experiments. Contrary to what one would assume, a higher extent of fatty acid liberation did not enhance drug release. In other words, drug release does not seem to be driven by the extent of lipid digestion.

  13. Autophagy facilitates macrophage depots of sustained-release nanoformulated antiretroviral drugs.

    PubMed

    Gnanadhas, Divya Prakash; Dash, Prasanta K; Sillman, Brady; Bade, Aditya N; Lin, Zhiyi; Palandri, Diana L; Gautam, Nagsen; Alnouti, Yazen; Gelbard, Harris A; McMillan, JoEllyn; Mosley, R Lee; Edagwa, Benson; Gendelman, Howard E; Gorantla, Santhi

    2017-03-01

    Long-acting anti-HIV products can substantively change the standard of care for patients with HIV/AIDS. To this end, hydrophobic antiretroviral drugs (ARVs) were recently developed for parenteral administration at monthly or longer intervals. While shorter-acting hydrophilic drugs can be made into nanocarrier-encased prodrugs, the nanocarrier encasement must be boosted to establish long-acting ARV depots. The mixed-lineage kinase 3 (MLK-3) inhibitor URMC-099 provides this function by affecting autophagy. Here, we have shown that URMC-099 facilitates ARV sequestration and its antiretroviral responses by promoting the nuclear translocation of the transcription factor EB (TFEB). In monocyte-derived macrophages, URMC-099 induction of autophagy led to retention of nanoparticles containing the antiretroviral protease inhibitor atazanavir. These nanoparticles were localized within macrophage autophagosomes, leading to a 4-fold enhancement of mitochondrial and cell vitality. In rodents, URMC-099 activation of autophagy led to 50-fold increases in the plasma drug concentration of the viral integrase inhibitor dolutegravir. These data paralleled URMC-099-mediated induction of autophagy and the previously reported antiretroviral responses in HIV-1-infected humanized mice. We conclude that pharmacologic induction of autophagy provides a means to extend the action of a long-acting, slow, effective release of antiretroviral therapy.

  14. Site-Specific, Sustained Release of Drugs to the Brain

    NASA Astrophysics Data System (ADS)

    Bodor, Nicholas; Farag, Hassan H.; Brewster, Marcus E.

    1981-12-01

    A dihydropyridine-pyridinium salt type of redox system is used in a general and flexible method for site-specific or sustained delivery (or both) of drugs to the brain. A biologically active compound linked to a lipoidal dihydropyridine carrier easily penetrates the blood-brain barrier. Oxidation of the carrier part in vivo to the ionic pyridinium salt prevents its elimination from the brain, while elimination from the general circulation is accelerated. Subsequent cleavage of the quaternary carrier-drug species results in sustained delivery of the drug in the brain and facile elimination of the carrier part.

  15. A drug release study from hydroxypropylmethylcellulose (HPMC) matrices using QSPR modeling.

    PubMed

    Ghafourian, Taravat; Gafourian, Taravat; Safari, Arezoo; Adibkia, Khosro; Parviz, Fatemeh; Nokhodchi, Ali

    2007-12-01

    This investigation is aimed at characterization of the mode of release from two different substitution types of HPMC and the effect of chemical structure of drugs using the QSPR (Quantitative - Structure-Property Relationship) technique. To this end, release profiles of HPMC matrices of several drugs containing the same formulation and compressed at a constant pressure were studied. QSPR method was used to establish statistically significant relationships between release parameters and the structural descriptors. Structural descriptors consisted of molecular mechanical, quantum mechanical and graph-theoretical parameters, as well as the partition coefficient and the aqueous solubility of the drugs. The results showed that the most important factors determining the release profile from both HPMC K4M and HPMC E4M matrices were the aqueous solubility of drugs (which could be substituted efficiently by dipole moment) and the size of the drug molecules. Comparison of drug release from matrices prepared using the two grades of HPMC showed very distinct differences for some drugs, as evaluated by the similarity factor. The results indicated that the source of the difference could be sought in the drug properties (as exemplified by the aqueous solubility and surface area) as well as the rate of erosion (that depends mainly on the polymer type).

  16. In-vitro release of acyclovir loaded Eudragit RLPO(®) nanoparticles for sustained drug delivery.

    PubMed

    Gandhi, Arijit; Jana, Sougata; Sen, Kalyan Kumar

    2014-06-01

    In this present study the possibility to develop Eudragit RLPO(®) based nanoparticles of acyclovir was investigated in order to increase its efficacy because acyclovir has oral bioavailability of only 10-20% thus showing erratic absorption and bioavailability behaviour. The nanoparticles were prepared by nanoprecipitation technique. Pluronic F68 was used as stabilizer. The nanoparticles were characterized by particle size, entrapment efficiency, DSC, SEM, FTIR and in-vitro drug release. It was found that as drug:polymer (Acyclovir:Eudragit RLPO(®)) ratio increased from 1:1.5 to 1:2, particle size was increased significantly and drug entrapment also increased but thereafter, further increase in drug: polymer ratio showed reduced or insignificant change in the drug entrapment efficiency. DSC results showed that in the prepared nanoaprticles, the drug was present in the amorphous phase and may have been homogeneously dispersed in the polymer matrix. In vitro drug release study of formulations showed release in 24h in the range 71.62±1.72 to 93.25±1.02%. The release was found to follow Higuchi model with non-Fickian diffusion mechanism for all batches. These preliminary results indicate that acyclovir loaded Eudragit RLPO(®) nanoparticles could be effective in sustaining drug release for a prolonged period.

  17. Subcellular tracking of drug release from carbon nanotube vehicles in living cells.

    PubMed

    Kang, Bin; Li, Jun; Chang, Shuquan; Dai, Mingzhu; Ren, Chao; Dai, Yaodong; Chen, Da

    2012-03-12

    The direct observation of drug release from carbon nanotube vehicles in living cells is realized through a unique two-dye labeling approach. Single-walled carbon nanotubes (SWNTs) are firstly marked with fluorescein isothiocyanate (FITC) to track their location and movement inside the cell. Then a fluorescent anticancer drug doxorubicin (DOX) is attached by means of π-stacking onto SWNTs. Delivered by SWNTs into cells, DOX will detach from the vehicle in an acidic environment due to the pH-dependent π-π stacking interaction between DOX and SWNTs. From observation of the two different kinds of fluorescence (green and red) that respectively represent the carrier SWNTs and drug DOX, the process of drug release inside the living cell can be monitored under a confocal microscope. Results show that the drug DOX detaches from SWNTs inside the lysosomes to yield free molecules and escape into the cytoplasm and finally into the nucleus, while the vehicle SWNTs are trapped inside the lysosomes, without entering the nucleus. The current observations confirm previously proposed mechanisms for drug/DOX release inside cells. The experimental establishment of drug-release mechanisms in living cells here might provide important insights for future design of new drug-delivery and release systems.

  18. Preparation and release of model drugs from thermally sensitive poly(N-isopropylacrylamide) based macrospheres.

    PubMed

    Lewis, G; Coughlan, D C; Lane, M E; Corrigan, O I

    2006-09-01

    Emulsion polymerization was employed to prepare poly(N-isopropylacrylamide) hydrogel spheres, which exhibited an LCST of 32 degrees C. The hydrogels were loaded with model drugs (benzoic acid (BA), sodium benzoate and diltiazem HCl (DHCl)) and release investigated at 25 degrees C and 37 degrees C. The temperature at which gel formation occurred was vital for successful hydrogel preparation, macrosphere formation not occurring when the temperature was close to the LCST. Sphere size increased on decreasing the stirring rate and on slowing the rate of addition of the aqueous phase. Pulsatile delivery was investigated using BA and DHCl. For both compounds a pulse was observed with a change in temperature. Pulsed release of the smaller model drug of lowest solubility, BA, was more successful. Drug release from hydrogel spheres was, therefore, found to be dependent on the physicochemical properties of the drugs, with pulsatile release of low molecular weight compounds, by temperature cycling, difficult to control.

  19. Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

    PubMed Central

    Hayashida, Kayoko; Higashi, Taishi; Kono, Daichi; Motoyama, Keiichi; Wada, Koki

    2014-01-01

    Summary Cyclodextrins (CDs) can form polypseudorotaxanes (PPRXs) with drugs or drug carriers possessing linear polymers such as polyethylene glycol (PEG). On the other hand, PEGylated liposomes have been utilized as a representative anticancer drug carrier. However, little is known about the formation of CD PPRX with PEGylated liposome. In the present study, we first report the formation of CD PPRX with PEGylated liposome and evaluate it as a sustained release drug carrier. PEGylated liposome encapsulating doxorubicin was disrupted by the addition of α-CD. Meanwhile, γ-CD included two PEG chains and/or one bending PEG chain of PEGylated liposome and formed PPRX without the disruption of the membrane integrity of the PEGylated liposome. Moreover, the release of doxorubicin and/or PEGylated liposome encapsulating doxorubicin from the PPRX was prolonged in accordance with the matrix type release mechanism. These findings suggest the potential of γ-CD PPRX as sustained release carriers for PEGylated liposome products. PMID:25550741

  20. Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier.

    PubMed

    Hayashida, Kayoko; Higashi, Taishi; Kono, Daichi; Motoyama, Keiichi; Wada, Koki; Arima, Hidetoshi

    2014-01-01

    Cyclodextrins (CDs) can form polypseudorotaxanes (PPRXs) with drugs or drug carriers possessing linear polymers such as polyethylene glycol (PEG). On the other hand, PEGylated liposomes have been utilized as a representative anticancer drug carrier. However, little is known about the formation of CD PPRX with PEGylated liposome. In the present study, we first report the formation of CD PPRX with PEGylated liposome and evaluate it as a sustained release drug carrier. PEGylated liposome encapsulating doxorubicin was disrupted by the addition of α-CD. Meanwhile, γ-CD included two PEG chains and/or one bending PEG chain of PEGylated liposome and formed PPRX without the disruption of the membrane integrity of the PEGylated liposome. Moreover, the release of doxorubicin and/or PEGylated liposome encapsulating doxorubicin from the PPRX was prolonged in accordance with the matrix type release mechanism. These findings suggest the potential of γ-CD PPRX as sustained release carriers for PEGylated liposome products.

  1. Serum Albumin Beads: An Injectable, Biodegradable System for the Sustained Release of Drugs

    NASA Astrophysics Data System (ADS)

    Lee, Timothy K.; Sokoloski, Theodore D.; Royer, Garfield P.

    1981-07-01

    Biologically active compounds were entrapped in cross-linked serum albumin microbeads. Injection of these drug-impregnated beads into rabbits produced no adverse immunological reactions. Sustained release (20 days) of progesterone was demonstrated in vivo.

  2. The production of volvox spheres and their potential application in multi-drugs encapsulation and release.

    PubMed

    Teong, Benjamin; Chang, Shwu Jen; Chuang, Chin Wen; Kuo, Shyh Ming; Manousakas, Ioannis

    2013-12-01

    Volvox sphere is a bio-mimicking concept of an innovative biomaterial structure of a sphere that contains smaller microspheres which then encapsulate chemicals, drugs and/or cells. The volvox spheres were produced via a high-voltage electrostatic field system, using alginate as the primary material. Encapsulated materials tested in this study include staining dyes, nuclear fast red and trypan blue, and model drugs, bovine serum albumin (BSA) and cytochrome c (CytC). The external morphology of the volvox spheres was observed via electron microscopy whereas the internal structure of the volvox spheres was observed via an optical microscope with the aid of the staining dyes, since alginate is colorless and transparent. The diameter of the microspheres was about 200 to 300 μm, whereas the diameter of the volvox spheres was about 1500 μm. Volvox spheres were durable, retaining about 95% of their mass after 4 weeks. Factors affecting entrapment efficiency, such as temperature and concentration of the bivalent cross-linker, were compared followed by a 7-day in vitro release study. The encapsulation efficiency of CytC within the microspheres was higher at cold (~4°C) and warm (~50°C) temperatures whereas temperature has no obvious effect on the BSA encapsulation. High crosslinking concentration (25% w/v) of calcium chloride has resulted higher entrapment efficiency for BSA but not for CytC. Furthermore, volvox spheres showed a different release pattern of BSA and CytC when compared to microspheres encapsulating BSA and CytC. Despite the fact that the mechanisms behind remain unclear and further investigation is required, this study demonstrates the potential of the volvox spheres for drug delivery.

  3. Chitosan-genipin microspheres for the controlled release of drugs: clarithromycin, tramadol and heparin.

    PubMed

    Harris, Ruth; Lecumberri, Elena; Heras, Angeles

    2010-05-26

    The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1-10 microm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 °C for 5 h and with 5 mM genipin at 50 °C for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 °C, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

  4. Chitosan-Genipin Microspheres for the Controlled Release of Drugs: Clarithromycin, Tramadol and Heparin

    PubMed Central

    Harris, Ruth; Lecumberri, Elena; Heras, Angeles

    2010-01-01

    The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1–10 μm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 ºC for 5 h and with 5 mM genipin at 50 ºC for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 ºC, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs. PMID:20631867

  5. Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes.

    PubMed

    Schroeder, Avi; Kost, Joseph; Barenholz, Yechezkel

    2009-11-01

    Ultrasound is used in many medical applications, such as imaging, blood flow analysis, dentistry, liposuction, tumor and fibroid ablation, and kidney stone disruption. In the past, low frequency ultrasound (LFUS) was the main method to downsize multilamellar (micron range) vesicles into small (nano scale) unilamellar vesicles. Recently, the ability of ultrasound to induce localized and controlled drug release from liposomes, utilizing thermal and/or mechanical effects, has been shown. This review, deals with the interaction of ultrasound with liposomes, focusing mainly on the mechanical mechanism of drug release from liposomes using LFUS. The effects of liposome lipid composition and physicochemical properties, on one hand, and of LFUS parameters, on the other, on liposomal drug release, are addressed. Acoustic cavitation, in which gas bubbles oscillate and collapse in the medium, thereby introducing intense mechanical strains, increases release substantially. We suggest that the mechanism of release may involve formation and collapse of small gas nuclei in the hydrophobic region of the lipid bilayer during exposure to LFUS, thereby inducing the formation of transient pores through which drugs are released. Introducing PEG-lipopolymers to the liposome bilayer enhances responsivity to LFUS, most likely due to absorption of ultrasonic energy by the highly hydrated PEG headgroups. The presence of amphiphiles, such as phospholipids with unsaturated acyl chains, which destabilize the lipid bilayer, also increases liposome susceptibility to LFUS. Application of these principles to design highly LFUS-responsive liposomes is discussed.

  6. Surface Modifications of Titanium Implants by Multilayer Bioactive Coatings with Drug Delivery Potential: Antimicrobial, Biological, and Drug Release Studies

    NASA Astrophysics Data System (ADS)

    Ordikhani, Farideh; Zustiak, Silviya Petrova; Simchi, Abdolreza

    2016-04-01

    Recent strategies to locally deliver antimicrobial agents to combat implant-associated infections—one of the most common complications in orthopedic surgery—are gaining interest. However, achieving a controlled release profile over a desired time frame remains a challenge. In this study, we present an innovative multifactorial approach to combat infections which comprises a multilayer chitosan/bioactive glass/vancomycin nanocomposite coating with an osteoblastic potential and a drug delivery capacity. The bioactive drug-eluting coating was prepared on the surface of titanium foils by a multistep electrophoretic deposition technique. The adopted deposition strategy allowed for a high antibiotic loading of 1038.4 ± 40.2 µg/cm2. The nanocomposite coating exhibited a suppressed burst release with a prolonged sustained vancomycin release for up to 6 weeks. Importantly, the drug release profile was linear with respect to time, indicating a zero-order release kinetics. An in vitro bactericidal assay against Staphylococcus aureus confirmed that releasing the drug reduced the risk of bacterial infection. Excellent biocompatibility of the developed coating was also demonstrated by in vitro cell studies with a model MG-63 osteoblast cell line.

  7. Layered double hydroxides as effective carrier for anticancer drugs and tailoring of release rate through interlayer anions.

    PubMed

    Senapati, Sudipta; Thakur, Ravi; Verma, Shiv Prakash; Duggal, Shivali; Mishra, Durga Prasad; Das, Parimal; Shripathi, T; Kumar, Mohan; Rana, Dipak; Maiti, Pralay

    2016-02-28

    Hydrophobic anticancer drug, raloxifene hydrochloride (RH) is intercalated into a series of magnesium aluminum layered double hydroxides (LDHs) with various charge density anions through ion exchange technique for controlled drug delivery. The particle nature of the LDH in presence of drug is determined through electron microscopy and surface morphology. The release of drug from the RH intercalated LDHs was made very fast or sustained by altering the exchangeable anions followed by the modified Freundlich and parabolic diffusion models. The drug release rate is explained from the interactions between the drug and LDHs along with order-disorder structure of drug intercalated LDHs. Nitrate bound LDH exhibits greater interaction with drug and sustained drug delivery against the loosely interacted phosphate bound LDH-drug, which shows fast release. Cell viability through MTT assay suggests drug intercalated LDHs as better drug delivery vehicle for cancer cell line against poor bioavailability of the pure drug. In vivo study with mice indicates the differential tumor healing which becomes fast for greater drug release system but the body weight index clearly hints at damaged organ in the case of fast release system. Histopathological experiment confirms the damaged liver of the mice treated either with pure drug or phosphate bound LDH-drug, fast release system, vis-à-vis normal liver cell morphology for sluggish drug release system with steady healing rate of tumor. These observations clearly demonstrate that nitrate bound LDH nanoparticle is a potential drug delivery vehicle for anticancer drugs without any side effect.

  8. Release of Water Soluble Drugs from Dynamically Swelling POLY(2-HYDROXYETHYL Methacrylate - CO - Methacrylic Acid) Hydrogels.

    NASA Astrophysics Data System (ADS)

    Kou, Jim Hwai-Cher

    In this study, ionizable copolymers of HEMA and methacrylic acid (MA) are investigated for their potential use in developing pH dependent oral delivery systems. Because of the MA units, these gels swell extensively at high pH. Since solute diffusion in the hydrophilic polymers depends highly on the water content of the matrix, it is anticipated that the release rate will be modulated by this pH induced swelling. From a practical point of view, the advantage of the present system is that one can minimize drug loss in the stomach and achieve a programmed release in intestine. This approach is expected to improve delivery of acid labile drugs or drugs that cause severe gastrointestinal side effects. This work mainly focuses on the basic understanding of the mechanism involved in drug release from the poly(HEMA -co- MA) gels, especially under dynamic swelling conditions. Equilibrium swelling is first characterized since water content is the major determinant of transport properties in these gels. Phenylpropanolamine (PPA) is chosen as the model drug for the release study and its diffusion characteristics in the gel matrix determined. The data obtained show that the PPA diffusivity follows the free volume theory of Yasuda, which explains the accelerating effect of swelling on drug release. A mathematical model based on a diffusion mechanism has been developed to describe PPA release from the swelling gels. Based on this model, several significant conclusions can be drawn. First, the release rate can be modulated by the aspect ratio of the cylindrical geometry, and this has a practical implication in dosage form design. Second, the release rate can be lowered quite considerably if the dimensional increase due to swelling is significant. Consequently, it is the balance between the drug diffusivity increase and the gel dimensional growth that determines the release rate from the swelling matrix. Third, quasi-steady release kinetics, which are characteristic of swelling

  9. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    SciTech Connect

    Matteini, P; Ratto, F; Rossi, F; Pini, R

    2014-07-31

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  10. A novel sustained release drug-resin complex-based microbeads of ciprofloxacin HCl.

    PubMed

    Jain, Sunil K; Prajapati, Neeraj; Rajpoot, Kuldeep; Kumar, Amrish

    2016-12-01

    Objective A novel multiparticulate system for the gastro-mucoadhesive delivery of ciprofloxacin HCl (CFN) was developed with the help of ion-exchange resin to deal with urinary tract (UT) infections effectively. Materials and methods An optimized complex (resinate) of CFN with sodium polystyrene sulfonate USP resin was prepared and entrapped within microbeads of sodium alginate and pectin. The developed systems were evaluated for drug entrapment efficiency, percentage of mucoadhesion and in vitro release patterns in simulated gastric fluid (pH 1.2). Results and discussion The interaction of the resin complex and polycation via alginate was consequently supported the formation of polyelectrolyte complex membrane. The in vitro drug release studies demonstrate that formulation without drug-resin complex (NRB) released the drug more swiftly than formulation containing drug-resin complex (DRC). This controlled release pattern of drug, resin complex containing microbeads was owed to complexation between drug and resin. Conclusion Preliminary results from the study suggested that this drug-resin complex-entrapped microbeads can be used to incorporate other antibiotic drugs and could be effective against UT infection. Such developed formulation could be subjected to in vivo studies in future in order to prove their efficacy for such type of infections.

  11. Formulation parameters affecting the performance of coated gelatin capsules with pulsatile release profiles.

    PubMed

    Bussemer, T; Bodmeier, R

    2003-11-28

    The objective of this study was to develop and evaluate a rupturable pulsatile drug delivery system based on soft gelatin capsules with or without a swelling layer and an external water-insoluble but -permeable polymer coating, which released the drug after a lag time (rupturing of the external polymer coating). The swelling of the gelatin capsule itself was insufficient to rupture the external polymer coating, an additional swelling layer was applied between the capsule and the polymer coating. Croscarmellose sodium (Ac-Di-Sol) was more effective as a swelling agent than low and high molecular weight hydroxypropylmethyl cellulose (HPMC; E5 or K100M). Brittle polymers, such as ethyl cellulose (EC) and cellulose acetate propionate (CAPr), led to a better rupturing and therefore more complete drug release than the flexible polymer coating, Eudragit RS. The lag time of the release system increased with higher polymer coating levels and decreased with the addition of a hydrophilic pore-former, HPMC E5 and also with an increasing amount of the intermediate swelling layer. The water uptake of the capsules was linear until rupture and was higher with CAPr than with EC. Soft gelatin capsule-based systems showed shorter lag times compared to hard gelatin capsules because of the higher hardness/filling state of the soft gelatin capsules. The swelling pressure was therefore more directed to the external polymer coating with the soft gelatin capsules. Typical pulsatile drug release profiles were obtained at lower polymer coating levels, while the release was slower and incomplete at the higher coating levels. CAPr-coated capsules resulted in a more complete release than EC-coated capsules.

  12. Stimuli-free programmable drug release for combination chemo-therapy

    NASA Astrophysics Data System (ADS)

    Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan

    2016-06-01

    Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug

  13. In vitro release kinetics of antituberculosis drugs from nanoparticles assessed using a modified dissolution apparatus.

    PubMed

    Gao, Yuan; Zuo, Jieyu; Bou-Chacra, Nadia; Pinto, Terezinha de Jesus Andreoli; Clas, Sophie-Dorothee; Walker, Roderick B; Löbenberg, Raimar

    2013-01-01

    The aim of this study was to assess the in vitro release kinetics of antituberculosis drug-loaded nanoparticles (NPs) using a "modified" cylindrical apparatus fitted with a regenerated cellulose membrane attached to a standard dissolution apparatus (modifiedcylinder method). The model drugs that were used were rifampicin (RIF) and moxifloxacin hydrochloride (MX). Gelatin and polybutyl cyanoacrylate (PBCA) NPs were evaluated as the nanocarriers, respectively. The dissolution and release kinetics of the drugs from loaded NPs were studied in different media using the modified cylinder method and dialysis bag technique was used as the control technique. The results showed that use of the modified cylinder method resulted in different release profiles associated with unique release mechanisms for the nanocarrier systems investigated. The modified cylinder method also permitted discrimination between forced and normal in vitro release of the model drugs from gelatin NPs in the presence or absence of enzymatic degradation. The use of dialysis bag technique resulted in an inability to differentiate between the mechanisms of drug release from the NPs in these cases. This approach offers an effective tool to investigate in vitro release of RIF and MX from NPs, which further indicate that this technique can be used for performance testing of nanosized carrier systems.

  14. In Vitro Release Kinetics of Antituberculosis Drugs from Nanoparticles Assessed Using a Modified Dissolution Apparatus

    PubMed Central

    Gao, Yuan; Zuo, Jieyu; Bou-Chacra, Nadia; Pinto, Terezinha de Jesus Andreoli; Clas, Sophie-Dorothee; Walker, Roderick B.; Löbenberg, Raimar

    2013-01-01

    The aim of this study was to assess the in vitro release kinetics of antituberculosis drug-loaded nanoparticles (NPs) using a “modified” cylindrical apparatus fitted with a regenerated cellulose membrane attached to a standard dissolution apparatus (modifiedcylinder method). The model drugs that were used were rifampicin (RIF) and moxifloxacin hydrochloride (MX). Gelatin and polybutyl cyanoacrylate (PBCA) NPs were evaluated as the nanocarriers, respectively. The dissolution and release kinetics of the drugs from loaded NPs were studied in different media using the modified cylinder method and dialysis bag technique was used as the control technique. The results showed that use of the modified cylinder method resulted in different release profiles associated with unique release mechanisms for the nanocarrier systems investigated. The modified cylinder method also permitted discrimination between forced and normal in vitro release of the model drugs from gelatin NPs in the presence or absence of enzymatic degradation. The use of dialysis bag technique resulted in an inability to differentiate between the mechanisms of drug release from the NPs in these cases. This approach offers an effective tool to investigate in vitro release of RIF and MX from NPs, which further indicate that this technique can be used for performance testing of nanosized carrier systems. PMID:23936771

  15. Electrospun micelles/drug-loaded nanofibers for time-programmed multi-agent release.

    PubMed

    Yang, Guang; Wang, Jie; Li, Long; Ding, Shan; Zhou, Shaobing

    2014-07-01

    Combined therapy with drugs of different therapeutic effects is an effective way in the treatment of diseases and damaged tissues or organs. However, how to precisely control the release order, dose, and time of the drugs using vehicles is still a challenging task. In this work, for the first time, a study to develop a nanoscale multi-drug delivery system based on polymer micelle-enriched electrospun nanofibers is presented. The multi-drug delivery system is achieved, first, by the fabrication of hydrophobic curcumin encapsulated micelles assembled from biodegradable mPEG-PCL copolymer and, second, by the blending of the micelle powder with hydrophilic doxorubicin in polyvinyl alcohol solution, followed by simply electrospinning this combination. Due to the different domains of the two drugs within the nanofibers, the release behaviors show a time-programmed release, and can be temporally and spatially regulated. In vitro tumor cell inhibition assay indicates that the delivery system possesses great potential in cancer chemotherapy.

  16. [Drug release of coated dental implant neck region to improve tissue integration].

    PubMed

    Wolf, Jens; Sternberg, Katrin; Behrend, Detlef; Schmitz, Klaus-Peter; von Schwanewede, Heinrich

    2009-08-01

    In order to improve tissue integration, the neck region of dental implants was coated with the biodegradable polymer poly (L-lactide) incorporating tetracycline, ibuprofen and the combination of both drugs using a solvent dip-coating process. Metallographic analysis, light microscopy and electron microscopy were used to detect the thickness range and the surface characteristics of the coatings. Cytotoxicity was evaluated using the tetrazolium colorimetric method with the fibroblast cell line L929. The in vitro drug release was measured in isotonic sodium chloride solution by UV spectroscopy. To explore if drug release is concentration-dependent, the total amount of drug was varied in the coating (20% wt, 30% wt and 40% wt). The results showed a continuous release of the embedded drugs in relevant dosage over a period of 6 months. In contrast to high tetracycline concentrations, high ibuprofen concentrations resulted in a decreased metabolic activity of the L929 fibroblasts.

  17. NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy

    NASA Astrophysics Data System (ADS)

    Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2015-09-01

    Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

  18. 3D printing of tablets containing multiple drugs with defined release profiles.

    PubMed

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Yang, Jing; Roberts, Clive J

    2015-10-30

    We have employed three-dimensional (3D) extrusion-based printing as a medicine manufacturing technique for the production of multi-active tablets with well-defined and separate controlled release profiles for three different drugs. This 'polypill' made by a 3D additive manufacture technique demonstrates that complex medication regimes can be combined in a single tablet and that it is viable to formulate and 'dial up' this single tablet for the particular needs of an individual. The tablets used to illustrate this concept incorporate an osmotic pump with the drug captopril and sustained release compartments with the drugs nifedipine and glipizide. This combination of medicines could potentially be used to treat diabetics suffering from hypertension. The room temperature extrusion process used to print the formulations used excipients commonly employed in the pharmaceutical industry. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray powder diffraction (XRPD) were used to assess drug-excipient interaction. The printed formulations were evaluated for drug release using USP dissolution testing. We found that the captopril portion showed the intended zero order drug release of an osmotic pump and noted that the nifedipine and glipizide portions showed either first order release or Korsmeyer-Peppas release kinetics dependent upon the active/excipient ratio used.

  19. Microfluidic Synthesis of Microfibers for Magnetic-Responsive Controlled Drug Release and Cell Culture

    PubMed Central

    Lin, Yung-Sheng; Huang, Keng-Shiang; Yang, Chih-Hui; Wang, Chih-Yu; Yang, Yuh-Shyong; Hsu, Hsiang-Chen; Liao, Yu-Ju; Tsai, Chia-Wen

    2012-01-01

    This study demonstrated the fabrication of alginate microfibers using a modular microfluidic system for magnetic-responsive controlled drug release and cell culture. A novel two-dimensional fluid-focusing technique with multi-inlets and junctions was used to spatiotemporally control the continuous laminar flow of alginate solutions. The diameter of the manufactured microfibers, which ranged from 211 µm to 364 µm, could be well controlled by changing the flow rate of the continuous phase. While the model drug, diclofenac, was encapsulated into microfibers, the drug release profile exhibited the characteristic of a proper and steady release. Furthermore, the diclofenac release kinetics from the magnetic iron oxide-loaded microfibers could be controlled externally, allowing for a rapid drug release by applying a magnetic force. In addition, the successful culture of glioblastoma multiforme cells in the microfibers demonstrated a good structural integrity and environment to grow cells that could be applied in drug screening for targeting cancer cells. The proposed microfluidic system has the advantages of ease of fabrication, simplicity, and a fast and low-cost process that is capable of generating functional microfibers with the potential for biomedical applications, such as drug controlled release and cell culture. PMID:22470443

  20. Poly(lactic acid)/chitosan hybrid nanoparticles for controlled release of anticancer drug.

    PubMed

    Wang, Wenlong; Chen, Shu; Zhang, Liang; Wu, Xi; Wang, Jiexin; Chen, Jian-Feng; Le, Yuan

    2015-01-01

    Poly(lactic acid) (PLA) is a kind of non-toxic biological materials with excellent absorbability, biocompatibility and biodegradability, which can be used for drug release, tissue engineering and surgical treatment applications. In this study, we prepared chitosan modified PLA nanoparticles as carriers for encapsulation of docetaxel by anti-solvent precipitation method. The morphology, particle size, zeta potential and composition of the PLA/chitosan were characterized by SEM, DLS, FTIR and XPS. As-prepared PLA/chitosan particles exhibited average size of 250 nm and showed very narrow distribution with polydispersity index of 0.098. Their large surface charge-ability was confirmed by zeta potential value of 53.9 mV. Docetaxel was released from PLA/chitosan nanoparticles with 40% initial burst release in 5 h and 70% cumulative release within 24 h, while from PLA nanoparticles 65% of docetaxel was released in 5h. In vitro drug release study demonstrated that PLA/chitosan nanoparticles prolonged drug release and decreased the burst release over the unmodified PLA nanoparticles. These results illustrated high potential of chitosan modified PLA nanoparticles for usage as anticancer drug carriers.

  1. Computational Studies of Drug Release, Transport and Absorption in the Human Intestines

    NASA Astrophysics Data System (ADS)

    Behafarid, Farhad; Brasseur, J. G.; Vijayakumar, G.; Jayaraman, B.; Wang, Y.

    2016-11-01

    Following disintegration of a drug tablet, a cloud of particles 10-200 μm in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the "fasting" vs. "fed" motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local 'quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. Supported by FDA.

  2. Fabrication of core-shell micro/nanoparticles for programmable dual drug release by emulsion electrospraying

    NASA Astrophysics Data System (ADS)

    Wang, Yazhou; Zhang, Yiqiong; Wang, Bochu; Cao, Yang; Yu, Qingsong; Yin, Tieying

    2013-06-01

    The study aimed at constructing a novel drug delivery system for programmable multiple drug release controlled with core-shell structure. The core-shell structure consisted of chitosan nanoparticles as core and polyvinylpyrrolidone micro/nanocoating as shell to form core-shell micro/nanoparticles, which was fabricated by ionic gelation and emulsion electrospray methods. As model drug agents, Naproxen and rhodamine B were encapsulated in the core and shell regions, respectively. The core-shell micro/nanoparticles thus fabricated were characterized and confirmed by scanning electron microscope, transmission electron microscope, and fluorescence optical microscope. The core-shell micro/nanoparticles showed good release controllability through drug release experiment in vitro. It was noted that a programmable release pattern for dual drug agents was also achieved by adjusting their loading regions in the core-shell structures. The results indicate that emulsion electrospraying technology is a promising approach in fabrication of core-shell micro/nanoparticles for programmable dual drug release. Such a novel multi-drug delivery system has a potential application for the clinical treatment of cancer, tuberculosis, and tissue engineering.

  3. Inorganically modified diatomite as a potential prolonged-release drug carrier.

    PubMed

    Janićijević, Jelena; Krajišnik, Danina; Calija, Bojan; Dobričić, Vladimir; Daković, Aleksandra; Krstić, Jugoslav; Marković, Marija; Milić, Jela

    2014-09-01

    Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM-EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice. High adsorbent loading of the selected modified diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8h from both DAMD comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process.

  4. A predictive model for the release of slightly water-soluble drugs from HPMC matrices.

    PubMed

    Fu, X C; Wang, G P; Wang, Y H; Liang, W Q

    2004-08-01

    A model to predict the fraction of slightly water-soluble drug released as a function of release time (t, h), HPMC concentration (C(H), w/w), drug solubility in distilled water at 37 degrees C (C(s), g/100 mL), and volume of drug molecule (V, nm3) was derived when theophyline, tinidazole, and propylthiouracil were selected as model drugs. The model is log (M(t)/M(infinity)) = 0.8683 logt-0.1930C(s) logt + 0.5406V logt-1.227C(H) + 0.1594C(s) + 0.4423C(H)C(s) - 0.8655 (n = 130, r = 0.9969), where Mt is the amount of drug released at time t, Minfinity is the amount of drug released over a very long time, which corresponds in principle to the initial loading, n is the number of samples, and r is the correlation coefficient. The model was validated using sulfamethoxazole and satisfactory results were obtained. The model can be used to predict the release fraction of variousslightly water-soluble drugs from HPMC matrices having different polymer levels.

  5. Gene duplication and divergence affecting drug content in Cannabis sativa.

    PubMed

    Weiblen, George D; Wenger, Jonathan P; Craft, Kathleen J; ElSohly, Mahmoud A; Mehmedic, Zlatko; Treiber, Erin L; Marks, M David

    2015-12-01

    Cannabis sativa is an economically important source of durable fibers, nutritious seeds, and psychoactive drugs but few economic plants are so poorly understood genetically. Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid (THCA) in marijuana compared with cannabidiolic acid (CBDA) in hemp. Individuals in the resulting F2 population were assessed for differential expression of cannabinoid synthase genes and were used in linkage mapping. Genetic markers associated with divergent cannabinoid phenotypes were identified. Although phenotypic segregation and a major quantitative trait locus (QTL) for the THCA/CBDA ratio were consistent with a simple model of codominant alleles at a single locus, the diversity of THCA and CBDA synthase sequences observed in the mapping population, the position of enzyme coding loci on the map, and patterns of expression suggest multiple linked loci. Phylogenetic analysis further suggests a history of duplication and divergence affecting drug content. Marijuana is distinguished from hemp by a nonfunctional CBDA synthase that appears to have been positively selected to enhance psychoactivity. An unlinked QTL for cannabinoid quantity may also have played a role in the recent escalation of drug potency.

  6. Preparation and controlled release of mesoporous MCM-41/propranolol hydrochloride composite drug.

    PubMed

    Zhai, Qing-Zhou

    2013-01-01

    This article used MCM-41 as a carrier for the assembly of propranolol hydrochloride by the impregnation method. By means of chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and low-temperature N(2) adsorption-desorption at 77 K, the characterization was made for the prepared materials. The propranolol hydrochloride guest assembly capacity was 316.20 ± 0.31 mg/g (drug/MCM-41). Powder XRD test results indicated that during the process of incorporation, the frameworks of the MCM-41 were not destroyed and the crystalline degrees of the host-guest nanocomposite materials prepared still remained highly ordered. Characterization by SEM and TEM showed that the composite material presented spherical particle and the average particle size of composite material was 186 nm. FT-IR spectra showed that the MCM-41 framework existed well in the (MCM-41)-propranolol hydrochloride composite. Low-temperature nitrogen adsorption-desorption results at 77 K showed that the guest partially occupied the channels of the molecular sieves. Results of the release of the prepared composite drug in simulated body fluid indicated that the drug can release up to 32 h and its maximum released amount was 99.20 ± 0.11%. In the simulated gastric juice release pattern of drug, the maximum time for the drug release was discovered to be 6 h and the maximum cumulative released amount of propranolol hydrochloride was 45.13 ± 0.23%. The drug sustained-release time was 10 h in simulated intestinal fluid and the maximum cumulative released amount was 62.05 ± 0.13%. The prepared MCM-41 is a well-controlled drug delivery carrier.

  7. Zero-Order Antibiotic Release from Multilayer Contact Lenses: Nonuniform Drug and Diffusivity Distributions Produce Constant-Rate Drug Delivery.

    PubMed

    Guzman, Gustavo; Es-Haghi, Siamak Shams; Nugay, Turgut; Cakmak, Mukerrem

    2017-02-01

    A novel approach to zero-order constant-rate drug delivery from contact lenses is presented. Quasi-Case II non-Fickian transport is achieved by nonuniform drug and diffusivity distributions within three-layer bimodal amphiphilic conetworks (β-APCNs). The center layer is a highly oxygen permeable β-APCN matrix, which contains the drug and exhibits a high drug diffusivity. The outer β-APCN layers contain no-drug and are loaded with vitamin E, which slows diffusion. In contrast to single-layer neat-polymer and vitamin E-loaded films that display first-order "burst" kinetics, it is demonstrated experimentally and by modeling that the combined effect of nonuniform distribution of drug loading and diffusion constants within the three-layer lens maintains low local drug concentration at the lens-fluid interface and yields zero-order drug delivery. The release rates of topical antibiotics provide constant-rate therapeutic-level delivery with appropriate oxygen permeability for at least 30 h, at which time ≈25% of the drug was released.

  8. [Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release].

    PubMed

    Leonova, M V; Maneshina, O A; Belousov, Iu B

    2010-01-01

    Review oral modified release drug forms of beta-adrenoblocker metoprolol which is used in arterial hypertension and ischemic heart disease is presented. Metoprolol has salts such as tartrate which is used for production of immediate release (IR) and sustained release (SR) forms and succinate used for production of controlled release form (CR/XL). Metoprolol SR has monolith matrix type, metoprolol CR/XL-system of multiple pellets. Effect of metoprolol tartrate (IR) on mortality was demonstrated in a number of studies in patients with arterial hypertension (AH) (MAPHY), myocardial infarction (SMT, GMT, MIAMI), dilated cardiomyopathy and heart failure (MDC). Studies of efficacy of metoprolol SR are scarce. Antihypertensive efficacy of metoprolol SR in patients with AH did not exceed that of a metoprolol IR or CR/XL. First retrospective analysis of efficacy of metoprolol tartrate and succinate (CR/XL) in patients after myocardial infarction allowed to obtain comparable results of 34% mortality lowering. In a prospective study in patients with chronic heart failure (COMET) metoprolol tartrate IR was not superior to carvedilol when mortality lowering was concerned. At the same time administration of controlled release metoprolol (CR/XL) in 2 large clinical trials (RESOLVD, MERITAHF) was advantageous in patients with chronic heart failure relative to lowering of mortality and rate of hospitalizations. A novel controlled release form of metoprolol has been created as a tartrate salt on the basis of pellet technology (CD/ERT) and its bioequivalence to metoprolol CR/XL has been proved.

  9. Evaluating the effects of crystallinity in new biocompatible polyester nanocarriers on drug release behavior.

    PubMed

    Karavelidis, Vassilios; Karavas, Evangelos; Giliopoulos, Dimitrios; Papadimitriou, Sofia; Bikiaris, Dimitrios

    2011-01-01

    Four new polyesters based on 1,3-propanediol and different aliphatic dicarboxylic acids were used to prepare ropinirole HCl-loaded nanoparticles. The novelty of this study lies in the use of polyesters with similar melting points but different degrees of crystallinity, varying from 29.8% to 67.5%, as drug nanocarriers. Based on their toxicity to human umbilical vein endothelial cells, these aliphatic polyesters were found to have cytotoxicity similar to that of polylactic acid and so may be considered as prominent drug nanocarriers. Drug encapsulation in polyesters was performed via an emulsification/solvent evaporation method. The mean particle size of drug-loaded nanoparticles was 164-228 nm, and the drug loading content was 16%-23%. Wide angle X-ray diffraction patterns showed that ropinirole HCl existed in an amorphous state within the nanoparticle polymer matrices. Drug release diagrams revealed a burst effect for ropinirole HCl in the first 6 hours, probably due to release of drug located on the nanoparticle surface, followed by slower release. The degree of crystallinity of the host polymer matrix seemed to be an important parameter, because higher drug release rates were observed in polyesters with a low degree of crystallinity.

  10. Evaluating the effects of crystallinity in new biocompatible polyester nanocarriers on drug release behavior

    PubMed Central

    Karavelidis, Vassilios; Karavas, Evangelos; Giliopoulos, Dimitrios; Papadimitriou, Sofia; Bikiaris, Dimitrios

    2011-01-01

    Four new polyesters based on 1,3-propanediol and different aliphatic dicarboxylic acids were used to prepare ropinirole HCl-loaded nanoparticles. The novelty of this study lies in the use of polyesters with similar melting points but different degrees of crystallinity, varying from 29.8% to 67.5%, as drug nanocarriers. Based on their toxicity to human umbilical vein endothelial cells, these aliphatic polyesters were found to have cytotoxicity similar to that of polylactic acid and so may be considered as prominent drug nanocarriers. Drug encapsulation in polyesters was performed via an emulsification/solvent evaporation method. The mean particle size of drug-loaded nanoparticles was 164–228 nm, and the drug loading content was 16%–23%. Wide angle X-ray diffraction patterns showed that ropinirole HCl existed in an amorphous state within the nanoparticle polymer matrices. Drug release diagrams revealed a burst effect for ropinirole HCl in the first 6 hours, probably due to release of drug located on the nanoparticle surface, followed by slower release. The degree of crystallinity of the host polymer matrix seemed to be an important parameter, because higher drug release rates were observed in polyesters with a low degree of crystallinity. PMID:22162659

  11. Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

    ERIC Educational Resources Information Center

    Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

    2010-01-01

    A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

  12. Polypyrrole nanoparticles for tunable, pH-sensitive and sustained drug release

    NASA Astrophysics Data System (ADS)

    Samanta, Devleena; Meiser, Jana L.; Zare, Richard N.

    2015-05-01

    We report the development of a generalized pH-sensitive drug delivery system that can release any charged drug preferentially at the pH range of interest. Our system is based on polypyrrole nanoparticles (PPy NPs), synthesized via a simple one-step microemulsion technique. These nanoparticles are highly monodisperse, stable in solution over the period of a month, and have good drug loading capacity (~15 wt%). We show that PPy NPs can be tuned to release drugs at both acidic and basic pH by varying the pH, the charge of the drug, as well as by adding small amounts of charged amphiphiles. Moreover, these NPs may be delivered locally by immobilizing them in a hydrogel. Our studies show encapsulation within a calcium alginate hydrogel results in sustained release of the incorporated drug for more than 21 days. Such a nanoparticle-hydrogel composite drug delivery system is promising for treatment of long-lasting conditions such as cancer and chronic pain which require controlled, localized, and sustained drug release.

  13. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... gonadotropin releasing factor analog-diphtheria toxoid conjugate injectable solution. DATES: This rule is...: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The authority citation for...

  14. Composite of magnetic drug carriers with thermo-responsive polymer for controlled drug release

    NASA Astrophysics Data System (ADS)

    Liu, Jia; Kitamoto, Yoshitaka

    2016-02-01

    The present paper describes organic/inorganic composite nanoparticles (CNPs) with a thermal response for biomedical applications. The composite nanoparticles are composed of a thermo-responsive polymer shell of hydroxypropyl cellulose (HPC) and a magnetic FeOx/silica core that exhibits a heat-generation capability against alternating magnetic fields. The heat-generation capability of the FeOx core was improved by modifying the synthesis process of the NPs to oxidize nonmagnetic FeO to magnetic Fe3O4. The HPC shell is observed by transmission electron microscopy after coating FeOx/silica NPs with HPC; the coating is confirmed by the increase of the hydrodynamic size of NPs and the weight loss with thermogravimetry. The FeOx/silica/HPC composite NPs exhibit a thermal response, which is confirmed by the temperature-dependent hydrodynamic size of the NPs. These results indicate that the thermo-responsive FeOx/silica/HPC composite particles have a potential as a drug carrier with a capability of controlled release.

  15. Relationship between diffusivity of water molecules inside hydrating tablets and their drug release behavior elucidated by magnetic resonance imaging.

    PubMed

    Kikuchi, Shingo; Onuki, Yoshinori; Kuribayashi, Hideto; Takayama, Kozo

    2012-01-01

    We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.

  16. Photoresponsive coumarin-tethered multifunctional magnetic nanoparticles for release of anticancer drug.

    PubMed

    Karthik, S; Puvvada, Nagaprasad; Kumar, B N Prashanth; Rajput, Shashi; Pathak, Amita; Mandal, Mahitosh; Singh, N D Pradeep

    2013-06-12

    Recently, photoresponsive nanoparticles have received significant attention because of their ability to provide spatial and temporal control over the drug release. In the present work, we report for the first time photoresponsive multifunctional magnetic nanoparticles (MNPs) fabricated using coumarin-based phototrigger and Fe/Si MNPs for controlled delivery of anticancer drug chlorambucil. Further, newly fabricated photoresponsive multifunctional MNPs were also explored for cell luminescence imaging. In vitro biological studies revealed that coumarin tethered Fe/Si MNPs of ~9 nm size efficiently delivered the anticancer drug chlorambucil into cancer cells and thereby improving the drug action to kill the cancer cells upon irradiation. Such multifunctional MNPs with strong fluorescence, good biocompatibility and efficient photocontrolled drug release ability will be of great benefit in the construction of light-activated multifunctional nano drug delivery systems.

  17. Influence of plasticizer level on the drug release from sustained release film coated and hot-melt extruded dosage forms.

    PubMed

    Zhu, Yucun; Mehta, Ketan A; McGinity, James W

    2006-01-01

    In the current study, the influence of plasticizer level on drug release was investigated for solid dosage forms prepared by hot-melt extrusion and film coating. The properties of two highly water-soluble compounds, diltiazem hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water-soluble drug, indomethacin (IDM), were investigated in the melt extrudates containing either Eudragit RSPO or Eudragit RD 100 and triethyl citrate (TEC) as the plasticizer. In addition, pellets containing DTZ were film coated with Eudragit RS 30D and varying levels of TEC using a fluidized bed coating unit. Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM exhibited a plasticization effect on the acrylic polymers, whereas no plasticizing effect by DTZ on Eudragit RSPO was observed. Thermogravimetric analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit RSPO and TEC at 140 degrees C, the maximum temperature used in the hot-melt extrusion process. The chemical stability of DTZ and IDM in the extrudate following hot-melt processing was determined by high pressure liquid chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt extrudates increased with an increase in the TEC level in the formulations, while the release rate of DTZ from the Eudragit RS 30D-coated pellets decreased with an increase in TEC in the coating dispersion. This phenomenon was due to the formation of a reservoir polymeric structure as a result of the thermal stress and shear stress involved in the hot-melt extrusion process regardless of the TEC level. In contrast, coalescence of the polymer particles in the film coating process was enhanced with higher levels of TEC, as demonstrated by scanning electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt extrudate formulation had no influence on the drug release rate as the drug release rate was controlled by drug diffusion through the inside of the polymeric

  18. Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates-Part I.

    PubMed

    Mehta, R; Teckoe, J; Schoener, C; Workentine, S; Ferrizzi, D; Rajabi-Siahboomi, A

    2016-12-01

    Ethylcellulose is one of the most commonly used polymers to develop reservoir type extended release multiparticulate dosage forms. For multiparticulate extended release dosage forms, the drug release is typically governed by the properties of the barrier membrane coating. The ICH Pharmaceutical Development Guideline (ICH Q8) requires an understanding of the influence of critical material attributes and critical process parameters on the drug release of a pharmaceutical product. Using this understanding, it is possible to develop robust formulations with consistent drug release characteristics. Critical material attributes for ethylcellulose were evaluated, and polymer molecular weight variation (viscosity) was considered to be the most critical attribute that can impact drug release. To investigate the effect of viscosity variation within the manufacturer's specifications of ethylcellulose, extended release multiparticulate formulations of two model drugs, metoprolol tartrate and acetaminophen, were developed using ETHOCEL™ as the rate controlling polymer. Quality by Design (QbD) samples of ETHOCEL Std. 10, 20, and 100 Premium grades representing the low, medium, and high molecular weight (viscosity) material were organically coated onto drug layered multiparticulates to a 15% weight gain (WG). The drug release was found to be similar (f 2 > 50) for both metoprolol tartrate and acetaminophen multiparticulates at different coating weight gains of ethylcellulose, highlighting consistent and robust drug release performance. The use of ETHOCEL QbD samples also serves as a means to develop multiparticulate dosage formulations according to regulatory guidelines.

  19. [Release characteristics in vitro and pharmacokinetics of da chuanxiong fang multiunit drug delivery system in rats].

    PubMed

    Wei, Yuan-feng; Zhang, Ning; Lin, Xiao; Feng, Yi

    2011-09-01

    The drug release characteristics ofDa Chuanxiong Fang multiunit drug delivery system (DCXFMDDS) in vivo and in vitro were evaluated. Ferulic acid (FA) and senkyunolide I (SI) were used as marker components, which were two of the effective components of Da Chuanxiong Fang. And their contents were determined by HPLC. Drug release characteristics in vitro of DCXFMDDS and Da Chuanxiong pills and pharmacokinetics characteristics of DCXFMDDS and Da Chuanxiong Fang active fraction (DCXFAF) in rats were compared. It was obvious that FA released from the DCXFMDDS in a sustained fashion but SI in a fast fashion both in vitro and in vivo. The releasing process and the releasing mechanism of FA and SI from DCXFMDDS were different, but the AUC value indicated that compared with DCXFAF the extent of absorption of FA and SI from DCXFMDDS was increased. Though from the same multiunit drug delivery system, FA an SI had different drug release characteristics both in vitro and in vivo, and that may be one of the reason why DCXFMDDS has the good properties such as rapid and long-lasting effect and high efficiency.

  20. Quantifying the effect size of changing environmental controls on carbon release from permafrost-affected soils

    NASA Astrophysics Data System (ADS)

    Schaedel, C.; Bader, M. K. F.; Schuur, E. A. G.; Bracho, R. G.; Capek, P.; De Baets, S. L.; Diakova, K.; Ernakovich, J. G.; Hartley, I. P.; Iversen, C. M.; Kane, E. S.; Knoblauch, C.; Lupascu, M.; Natali, S.; Norby, R. J.; O'Donnell, J. A.; Roy Chowdhury, T.; Santruckova, H.; Shaver, G. R.; Sloan, V. L.; Treat, C. C.; Waldrop, M. P.

    2014-12-01

    High-latitude surface air temperatures are rising twice as fast as the global mean, causing permafrost to thaw and thereby exposing large quantities of previously frozen organic carbon (C) to microbial decomposition. Increasing temperatures in high latitude ecosystems not only increase C emissions from previously frozen C in permafrost but also indirectly affect the C cycle through changes in regional and local hydrology. Warmer temperatures increase thawing of ice-rich permafrost, causing land surface subsidence where soils become waterlogged, anoxic conditions prevail and C is released in form of anaerobic CO2 and CH4. Although substrate quality, physical protection, and nutrient availability affect C decomposition, increasing temperatures and changes in surface and sub-surface hydrology are likely the dominant factors affecting the rate and form of C release from permafrost; however, their effect size on C release is poorly quantified. We have compiled a database of 24 incubation studies with soils from active layer and permafrost from across the entire permafrost zone to quantify a) the effect size of increasing temperatures and b) the changes from aerobic to anaerobic environmental soil conditions on C release. Results from two different meta-analyses show that a 10°C increase in temperature increased C release by a factor of two in boreal forest, peatland and tundra ecosystems. Under aerobic incubation conditions, soils released on average three times more C than under anaerobic conditions with large variation among the different ecosystems. While peatlands showed similar amounts of C release under aerobic and anaerobic soil conditions, tundra and boreal forest ecosystems released up to 8 times more C under anoxic conditions. This pan-arctic synthesis shows that boreal forest and tundra soils will have a larger impact on climate change when newly thawed permafrost C decomposes in an aerobic environment compared to an anaerobic environment even when

  1. Assessment of laser-induced release of drugs from liposomes: An in vitro study

    SciTech Connect

    Khoobehi, B.; Char, C.A.; Peyman, G.A. )

    1990-01-01

    We evaluated the characteristics of laser-induced release of an antimetabolite (cytosine arabinoside) from temperature-sensitive liposomes. Previous work had shown that a laser would induce breakdown of liposomes when a dye was encapsulated within the liposomes. The present investigation was performed to determine if release could be induced from liposomes that did not contain dye. In vitro, dynamic studies of the release of the drug from liposomes diluted in blood (flowing in a capillary tube at 40 microns/min) were conducted using an argon dye laser operating either in the blue-green mode (488/514 nm) or in the dye mode (577 nm). A radio-labeled marker was used to monitor the drug release. The results showed that the drug could indeed be released from liposomes that did not contain dye, at energy levels that are not likely to be harmful to the tissue. At identical power levels, the release of the drug was greater at 577 nm than at 488/514 nm, probably owing to the greater light absorbance of hemoglobin at the longer wavelength. The results indicate the potential for the site-specific release of a variety of molecules in the ocular vasculature.

  2. Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers

    PubMed Central

    Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

    2012-01-01

    Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid–ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids. PMID:25755991

  3. Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers.

    PubMed

    Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

    2012-01-01

    Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid-ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids.

  4. Review on Medusa:a polymer-based sustained release technology for protein and peptide drugs.

    PubMed

    Chan, Y-P; Meyrueix, R; Kravtzoff, R; Nicolas, F; Lundstrom, K

    2007-07-01

    The polymer-based Medusa system (Flamel Technologies) has been designed for slow release of therapeutic proteins and peptides. The Medusa II consists of a poly L-glutamate backbone grafted with hydrophobic alpha-tocopherol molecules, creating a colloidal suspension of nanoparticles (10 - 50 nm) in water. The sustained drug release is based on reversible drug interactions with hydrophobic nanodomains within the nanoparticles. In vivo, it is suggested that the therapeutic protein is displaced by endogenous proteins present in physiological fluids, leading to a slow drug release. The peak concentration is dramatically decreased and the protein release substantially extended. The Medusa technology has been applied to subcutaneous injection for several therapeutic proteins, such as IL-2 and IFN-alpha(2b), in animal models (rats, dogs, monkeys) and clinical trials in renal cancer (IL-2) and hepatitis C (IFN-alpha(2b)) patients.

  5. Tunable biphasic drug release from ethyl cellulose nanofibers fabricated using a modified coaxial electrospinning process

    NASA Astrophysics Data System (ADS)

    Li, Chen; Wang, Zhuan-Hua; Yu, Deng-Guang; Williams, Gareth R.

    2014-05-01

    This manuscript reports a new type of drug-loaded core-shell nanofibers that provide tunable biphasic release of quercetin. The nanofibers were fabricated using a modified coaxial electrospinning process, in which a polyvinyl chloride (PVC)-coated concentric spinneret was employed. Poly (vinyl pyrrolidone) (PVP) and ethyl cellulose (EC) were used as the polymer matrices to form the shell and core parts of the nanofibers, respectively. Scanning and transmission electron microscopy demonstrated that the nanofibers had linear morphologies and core-shell structures. The quercetin was found to be present in the nanofibers in the amorphous physical status, on the basis of X-ray diffraction results. In vitro release profiles showed that the PVP shell very rapidly freed its drug cargo into the solution, while the EC core provided the succedent sustained release. Variation of the drug loading permitted the release profiles to be tuned.

  6. Externally controlled drug release using a gold nanorod contained composite membrane

    NASA Astrophysics Data System (ADS)

    Kim, Kibeom; Jo, Min-Chul; Jeong, Sundo; Palanikumar, L.; Rotello, Vincent M.; Ryu, Ja-Hyoung; Park, Myoung-Hwan

    2016-06-01

    Versatile drug delivery devices using nanoporous membranes consisting of gold nanorods and dendrimers have been demonstrated to provide light-triggered on-demand pulsatile release from a reservoir containing highly enriched therapeutics for a real patient's needs. The drug release rate is directly correlated with the temperature increase and irradiated energy of a near-IR laser in both static and fluidic devices. This biocompatible platform for on-demand control was further confirmed by in vitro experiments. Interestingly, different responses to stimuli were obtained from each drug in the absence and presence of NIR light, indicating the versatile potential of our on-demand drug delivery system in less-invasive therapies requiring multi-drug delivery strategies. The enhanced delivery system will improve therapeutic efficacy and reduce side effects through regulation of plasma drug profiles.Versatile drug delivery devices using nanoporous membranes consisting of gold nanorods and dendrimers have been demonstrated to provide light-triggered on-demand pulsatile release from a reservoir containing highly enriched therapeutics for a real patient's needs. The drug release rate is directly correlated with the temperature increase and irradiated energy of a near-IR laser in both static and fluidic devices. This biocompatible platform for on-demand control was further confirmed by in vitro experiments. Interestingly, different responses to stimuli were obtained from each drug in the absence and presence of NIR light, indicating the versatile potential of our on-demand drug delivery system in less-invasive therapies requiring multi-drug delivery strategies. The enhanced delivery system will improve therapeutic efficacy and reduce side effects through regulation of plasma drug profiles. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00362a

  7. A Microparticle/Hydrogel Combination Drug-Delivery System for Sustained Release of Retinoids

    PubMed Central

    Gao, Song-Qi; Maeda, Tadao; Okano, Kiichiro; Palczewski, Krzysztof

    2012-01-01

    Purpose. To design and develop a drug-delivery system containing a combination of poly(d,l-lactide-co-glycolide) (PLGA) microparticles and alginate hydrogel for sustained release of retinoids to treat retinal blinding diseases that result from an inadequate supply of retinol and generation of 11-cis-retinal. Methods. To study drug release in vivo, either the drug-loaded microparticle–hydrogel combination was injected subcutaneously or drug-loaded microparticles were injected intravitreally into Lrat−/− mice. Orally administered 9-cis-retinoids were used for comparison and drug concentrations in plasma were determined by HPLC. Electroretinography (ERG) and both chemical and histologic analyses were used to evaluate drug effects on visual function and morphology. Results. Lrat−/− mice demonstrated sustained drug release from the microparticle/hydrogel combination that lasted 4 weeks after subcutaneous injection. Drug concentrations in plasma of the control group treated with the same oral dose rose to higher levels for 6−7 hours but then dropped markedly by 24 hours. Significantly increased ERG responses and a markedly improved retinal pigmented epithelium (RPE)–rod outer segment (ROS) interface were observed after subcutaneous injection of the drug-loaded delivery combination. Intravitreal injection of just 2% of the systemic dose of drug-loaded microparticles provided comparable therapeutic efficacy. Conclusions. Sustained release of therapeutic levels of 9-cis-retinoids was achieved in Lrat−/− mice by subcutaneous injection in a microparticle/hydrogel drug-delivery system. Both subcutaneous and intravitreal injections of drug-loaded microparticles into Lrat−/− mice improved visual function and retinal structure. PMID:22918645

  8. Drug Release Characteristics and Tissue Distribution of Rifapentine Polylactic Acid Sustained-Release Microspheres in Rabbits after Paravertebral Implantation

    PubMed Central

    Zhang, Zheng; Wu, Linbo; Li, Haijian; Long, Zhicheng; Song, Xinghua

    2016-01-01

    Background Rates of drug-resistant tuberculosis (TB) and TB associated with human immunodeficiency virus (HIV) infection have increased dramatically, intensifying challenges in TB control. New formulations of TB treatment drugs that control drug release and increase local drug concentrations will have a significant impact on mitigating the toxic side effects and increasing the clinical efficacy of anti-TB drugs. Objectives The aim was to observe the sustained release characteristics of rifapentine polylactic acid sustained-release microspheres in vivo and the accumulation of rifapentine in other tissues following paravertebral implantation. Methods This study is a basic animal experimental study that began on July 17, 2014 in the Fifth Affiliated hospital of Xinjiang Medical University. One hundred and eight New Zealand white rabbits (weighing 2.8 - 3.0 kg, male and female, China) were randomly divided into three groups of 36 rabbits each. Blood and tissue samples from the liver, lungs, kidneys, vertebrae, and paravertebral muscle were collected at different time points post-surgery. High performance liquid chromatography (HPLC) analysis with a biological internal standard was used to determine the drug concentrations in samples. Results In group A, no significant differences in rifapentine concentrations in the liver were detected between any two time points (P > 0.05). However, the differences in rifapentine concentrations between day 10 and day 21 were statistically significant (P < 0.05); for days 21, 35, 46, and 60, the differences in rifapentine concentrations between two sequential time points were not statistically significant (P > 0.05). In group B, the differences in rifapentine concentration between days 3 and 10 in vertebral bone and in paravertebral muscles were statistically significant (P < 0.05). Rifapentine was detected in the vertebral bone tissue in the group C animals. The rifapentine concentrations between two sequential time points were

  9. Responsive copolymer–graphene oxide hybrid microspheres with enhanced drug release properties

    DOE PAGES

    Dong, Fuping; Firkowska-Boden, Izabela; Arras, Matthias M. L.; ...

    2017-01-13

    Here, the ability to integrate both high encapsulation efficiency and controlled release in a drug delivery system (DDS) is a highly sought solution to cure major diseases. However, creation of such a system is challenging. This study was aimed at constructing a new delivery system based on thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAm-co-PS) hollow microspheres prepared via two-step precipitation polymerization. To control the diffusion-driven drug release, the PNIPAAm-co-PS spheres were electrostatically coated with graphene oxide (GO) nanosheets. As a result of the coating the permeability of such copolymer-GO hybrid microspheres was reduced to the extent that suppressed the initial burst release and enabledmore » sustained drug release in in vitro testing. The hybrid microspheres showed improved drug encapsulation by 46.4% which was attributed to the diffusion barrier properties and -conjugated structure of GO. The system presented here is promising to advance, e.g., the anticancer drug delivery technologies by enabling sustained drug release and thus minimizing local and systemic side effects.« less

  10. Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets.

    PubMed

    Agarwal, Shweta; Murthy, R S R

    2015-01-01

    Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches.

  11. Magnetic field activated lipid–polymer hybrid nanoparticles for stimuli-responsive drug release

    PubMed Central

    Kong, Seong Deok; Sartor, Marta; Hu, Che-Ming Jack; Zhang, Weizhou; Zhang, Liangfang; Jin, Sungho

    2014-01-01

    Stimuli-responsive nanoparticles (SRNPs) offer the potential of enhancing the therapeutic efficacy and minimizing the side-effects of chemotherapeutics by controllably releasing the encapsulated drug at the target site. Currently controlled drug release through external activation remains a major challenge during the delivery of therapeutic agents. Here we report a lipid–polymer hybrid nanoparticle system containing magnetic beads for stimuli-responsive drug release using a remote radio frequency (RF) magnetic field. These hybrid nanoparticles show long-term stability in terms of particle size and polydispersity index in phosphate-buffered saline (PBS). Controllable loading of camptothecin (CPT) and Fe3O4 in the hybrid nanoparticles was demonstrated. RF-controlled drug release from these nanoparticles was observed. In addition, cellular uptake of the SRNPs into MT2 mouse breast cancer cells was examined. Using CPT as a model anticancer drug the nanoparticles showed a significant reduction in MT2 mouse breast cancer cell growth in vitro in the presence of a remote RF field. The ease of preparation, stability, and controllable drug release are the strengths of the platform and provide the opportunity to improve cancer chemotherapy. PMID:23149252

  12. On-demand controlled release of docetaxel from a battery-less MEMS drug delivery device.

    PubMed

    Pirmoradi, Fatemeh Nazly; Jackson, John K; Burt, Helen M; Chiao, Mu

    2011-08-21

    We report the development of a magnetically controlled MEMS device capable of on-demand release of defined quantities of an antiproliferative drug, docetaxel (DTX). Controlled release of DTX with a dosage suitable for the treatment of diabetic retinopathy has been achieved for 35 days. The device consists of a drug-loaded microreservoir (Ø6 mm ×∼550 μm), sealed by an elastic magnetic PDMS (polydimethylsiloxane) membrane (Ø6 mm × 40 μm) with a laser-drilled aperture (∼100 × 100 μm(2)). By applying a magnetic field, the magnetic PDMS membrane deforms, causing the discharge of the drug solution from the device. Controlled DTX release at a rate of 171 ± 16.7 ng per actuation interval has been achieved for 35 days using a 255 mT magnetic field. The background leakage of drug solution through the aperture was negligible at 0.053 ± 0.014 ng min(-1). The biological activity of the released drug was investigated using a cytotoxicity assay (cell apoptosis) for two cell lines, HUVEC (human umbilical vein endothelial cells) and PC3 (prostate cancer) cells. Reproducible release rates have been achieved and DTX within the PDMS MEMS reservoir maintains full pharmacological efficacy for more than two months. This device is a proof-of-concept development for targeted delivery of hydrophobic drugs such as DTX and other taxane-based agents that require accurate delivery in nanomolar concentrations.

  13. Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets

    PubMed Central

    Agarwal, Shweta; Murthy, R. S. R.

    2015-01-01

    Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches. PMID:26997698

  14. Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid) in Simulated Intestinal Fluids

    PubMed Central

    Knöös, Patrik

    2015-01-01

    A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated. PMID:26473964

  15. Effect of surfactant chain length on drug release kinetics from microemulsion-laden contact lenses.

    PubMed

    Maulvi, Furqan A; Desai, Ankita R; Choksi, Harsh H; Patil, Rahul J; Ranch, Ketan M; Vyas, Bhavin A; Shah, Dinesh O

    2017-03-31

    The effect of surfactant chain lengths [sodium caprylate (C8), Tween 20 (C12), Tween 80 (C18)] and the molecular weight of block copolymers [Pluronic F68 and Pluronic F 127] were studied to determine the stability of the microemulsion and its effect on release kinetics from cyclosporine-loaded microemulsion-laden hydrogel contact lenses in this work. Globule size and dilution tests (transmittance) suggested that the stability of the microemulsion increases with increase in the carbon chain lengths of surfactants and the molecular weight of pluronics. The optical transmittance of direct drug-laden contact lenses [DL-100] was low due to the precipitation of hydrophobic drugs in the lenses, while in microemulsion-laden lenses, the transmittance was improved when stability of the microemulsion was achieved. The results of in vitro release kinetics revealed that drug release was sustained to a greater extent as the stability of microemulsion was improved as well. This was evident in batch PF127-T80, which showed sustained release for 15days in comparison to batch DL-100, which showed release up to 7days. An in vivo drug release study in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC) with PF-127-T80 lenses (stable microemulsion) in comparison to PF-68-SC lenses (unstable microemulsion) and DL-100 lenses. This study revealed the correlation between the stability of microemulsion and the release kinetics of drugs from contact lenses. Thus, it was inferred that the stable microemulsion batches sustained the release of hydrophobic drugs, such as cyclosporine from contact lenses for an extended period of time without altering critical lens properties.

  16. Drug release assays from new chitosan/pHEMA membranes obtained by gamma irradiation

    NASA Astrophysics Data System (ADS)

    Casimiro, M. H.; Gil, M. H.; Leal, J. P.

    2007-12-01

    With the purpose of obtaining a biocompatible and microbiologically safe matrix that simultaneously could be used as wound dressing material and as a controlled drug release system, membranes with different thickness and different contents in chitosan and hydroxyethyl methacrylate (HEMA) have been prepared by γ irradiation from a 60Co source. Antibiotic release experiments were performed before or after irradiation over amoxicillin loaded chitosan/pHEMA membranes in physiological saline solution, and monitored by UV-Vis spectrometry. Results point out a fast amoxicillin release with similar release profile in all studied membranes. The amount of released drug was shown to be dependent on membranes network crosslinking due composition, radiation and membrane thickness.

  17. Extracellular control of intracellular drug release for enhanced safety of anti-cancer chemotherapy

    NASA Astrophysics Data System (ADS)

    Zhu, Qian; Qi, Haixia; Long, Ziyan; Liu, Shang; Huang, Zhen; Zhang, Junfeng; Wang, Chunming; Dong, Lei

    2016-06-01

    The difficulty of controlling drug release at an intracellular level remains a key challenge for maximising drug safety and efficacy. We demonstrate herein a new, efficient and convenient approach to extracellularly control the intracellular release of doxorubicin (DOX), by designing a delivery system that harnesses the interactions between the system and a particular set of cellular machinery. By simply adding a small-molecule chemical into the cell medium, we could lower the release rate of DOX in the cytosol, and thereby increase its accumulation in the nuclei while decreasing its presence at mitochondria. Delivery of DOX with this system effectively prevented DOX-induced mitochondria damage that is the main mechanism of its toxicity, while exerting the maximum efficacy of this anti-cancer chemotherapeutic agent. The present study sheds light on the design of drug delivery systems for extracellular control of intracellular drug delivery, with immediate therapeutic implications.

  18. Novel Salted Anionic-Cationic Polymethacrylate Polymer Blends for Sustained Release of Acidic And Basic Drugs.

    PubMed

    Obeidat, Wasfy M; Qasim, Duaa; Nokhodchi, Ali; Al-Jabery, Ahmad; Sallam, Al-Sayed

    2016-05-02

    Since a unique matrix tablet formulation that independently controls the release of various drug types is in a great demand, the objective of this research was to develop a sustained release matrix tablet as a universal dosage form using a binary mixture of the salt forms of Eudragit polymers rather than their interpolyelectrolyte complexes. Tablets were prepared by wet granulation and compressed at different compression forces, depending on drug type. Dissolution tests were conducted using USP XXII rotating paddle apparatus at 50 rpm at 37°C in consecutive pH stages. Tablets containing Ibuprofen (IB) as a model acidic drug and Metronidazole (MD) as a model basic drug showed controlled/sustained release behavior. For IB tablets containing 80% Ibuprofen and 5% (w/w) polymeric combination; the time for 50% of the drug release was about 24 hours compared to 8.5 hours for plain tablets containing 80% IB. In case of MD, the drug release extended to about 7 hours for tablets containing 80% MD and 5% (w/w) polymeric combination, compared to about 1 hour for plain tablets containing 80% MD. In terms of extending the release of medications, the dissolution profiles of the tablets containing polymeric salts forms were found to be statistically superior to tablets prepared by direct compression of the polymers in their powdered base forms, and superior to tablets containing the same polymers granulated using isopropyl alcohol. The findings indicated the significance of combining the polymers in their salt forms in controlling the release of various drug types from matrices.

  19. Diffusion-Controlled Drug Release From the Mesoporous Magnesium Carbonate Upsalite(®).

    PubMed

    Zhang, Peng; Zardán Gómez de la Torre, Teresa; Forsgren, Johan; Bergström, Christel A S; Strømme, Maria

    2016-02-01

    In vitro drug release from well-defined particle-size fractions of the mesoporous magnesium carbonate material Upsalite(®) was investigated in detail using ibuprofen, a biopharmaceutics classification system class II drug, as the model compound. The weight of loaded drug corresponded to 30% of the weight of the carrier and the pores were filled to approximately 80%. The incorporated ibuprofen was found to be in an amorphous state and was physisorbed, rather than chemisorbed, to the surfaces of the pore walls. In contrast to ibuprofen in mesoporous silica, there was no detectable drug on the outer surface of the carrier particles. Two ibuprofen doses were loaded into Upsalite(®) particles with size fractions ranging from 25 μm to more than 200 μm. The initial release rate was controlled by the particle size; the dissolution rate of the loaded ibuprofen during this period was more than four times faster than that of the crystalline drug. An extended-release period of about 24 h followed the initial rapid-release period. The features of this extended-release period were dependent on the total drug concentration in the release medium. Detailed analysis of the diffusion of ibuprofen in Upsalite(®) provided the ibuprofen diffusion coefficient (9.8 × 10(-8) cm(2)/s), the constrictivity of the diffusion process (0.47) and the tortuosity of the carrier (15). This relatively high tortuosity value indicates that Upsalite(®) can be used not only to enhance the dissolution rate of poorly soluble drugs but also as a carrier in sustained-release applications by using larger particle sizes or even pellets of the material.

  20. Interaction between DNA and Drugs Having Protonable Basic Groups: Characterization through Affinity Constants, Drug Release Kinetics, and Conformational Changes.

    PubMed

    Alarcón, Liliana P; Baena, Yolima; Manzo, Rubén H

    2017-01-04

    This paper reports the in vitro characterization of the interaction between the phosphate groups of DNA and the protonated species of drugs with basic groups through the determination of the affinity constants, the reversibility of the interaction, and the effect on the secondary structure of the macromolecule. Affinity constants of the counterionic condensation DNA-drug were in the order of 10⁶. The negative electrokinetic potential of DNA decreased with the increase of the proportion of loading drugs. The drugs were slowly released from the DNA-drug complexes and had release kinetics consistent with the high degree of counterionic condensation. The circular dichroism profile of DNA was not modified by complexation with atenolol, lidocaine, or timolol, but was significantly altered by the more lipophilic drugs benzydamine and propranolol, revealing modifications in the secondary structure of the DNA. The in vitro characterization of such interactions provides a physicochemical basis that would contribute to identify the effects of this kind of drugs in cellular cultures, as well as side effects observed under their clinical use. Moreover, this methodology could also be projected to the fields of intracellular DNA transfection and the use of DNA as a carrier of active drugs.

  1. Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate).

    PubMed

    Bohr, Adam; Wang, Yingya; Harmankaya, Necati; Water, Jorrit J; Baldursdottír, Stefania; Almdal, Kristoffer; Beck-Broichsitter, Moritz

    2017-02-23

    Poly(ethylene carbonate) (PEC) is an unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196 kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264.7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, eroding-controlled drug release pattern. Accordingly, the obtained in vitro degradation half-lives correlated well with the observed in vitro half-times of drug delivery (R(2)=0.96). Here, the PEC of the highest molecular weight resulted in the fastest degradation/drug release. When incubated with macrophages or implanted in animals, the degradation rate of PEC films superimposed the results of in vitro incubations with cholesterol esterase. Interestingly, SEM analysis indicated a distinct surface erosion process for enzyme-, macrophage- and in vivo-treated polymer films in a molecular weight-dependent manner. Overall, the molecular weight of surface-eroding PEC was identified as an essential parameter to control the spatial and temporal on-demand degradation and drug release from the employed delivery system.

  2. Polymeric matrices based on graft copolymers of PCL onto acrylic backbones for releasing antitumoral drugs.

    PubMed

    Abraham, Gustavo A; Gallardo, Alberto; San Román, Julio; Fernández-Mayoralas, Alfonso; Zurita, Mercedes; Vaquero, Jesús

    2003-03-15

    Graft copolymers of poly(epsilon-caprolactone) (PCL) on poly(dimethylacrylamide) (PDMAm), poly(methylmethacrylate) (PMMA), or on copolymers of poly(DMAm-co-MMA) have been synthesized and characterized by (1)H NMR spectroscopy, differential scanning calorimetry (DSC), and size exclusion chromatography (SEC). These partially biodegradable copolymer matrices have been proposed as drug delivery systems for the release of low-molecular-weight glycosides. Octyl-N-acetyl-6-O-[2,2-bis(hydroxymethyl)-3-hydroxypropyl]-alpha-D-glucosamide, a synthetic carbohydrate able to inhibit the proliferation of human malignant glioma cells in culture and transplanted glioma in rats was selected as drug model. The in vitro aqueous behavior of four drug-loaded and unloaded graft copolymers of different MMA: DMAm and PCL ratios has been analyzed performing swelling, degradation, and drug release experiments. An intimate dependence of the aqueous behavior with the composition has been found. The higher was the DMAm content, the higher was the hydrophilicity of the synthesized systems as well as the swelling, degradation, and drug release rate. In vivo experiments in pigs demonstrated the very good tolerance of drug-loaded implanted polymeric discs, and that >95% of the charged drug is released after 2 months' implantation.

  3. Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection

    NASA Astrophysics Data System (ADS)

    Bear, Joseph C.; Patrick, P. Stephen; Casson, Alfred; Southern, Paul; Lin, Fang-Yu; Powell, Michael J.; Pankhurst, Quentin A.; Kalber, Tammy; Lythgoe, Mark; Parkin, Ivan P.; Mayes, Andrew G.

    2016-09-01

    Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine.

  4. The synthesis and application involving regulation of the insoluble drug release from mesoporous silica nanotubes

    NASA Astrophysics Data System (ADS)

    Li, Jia; Wang, Yan; Zheng, Xin; Zhang, Ying; Sun, Changshan; Gao, Yikun; Jiang, Tongying; Wang, Siling

    2015-03-01

    Mesoporous silica nanotubes (SNT) were synthesized using hard template carbon nanotubes (CNT) with the aid of cetyltrimethyl ammonium bromide (CTAB) in a method, which was simple and inexpensive. Scanning electron microscopy, transmission electron microscopy and specific surface area analysis were employed to characterize the morphology and structure of SNT, and the formation mechanism of SNT was also examined by Fourier transform infrared spectroscopy. There are few published reports of the mesoporous SNT with large specific surface area applied in the drug delivery systems to improve the amount of drug loading. In addition, the structure of SNT allows investigators to control the drug particle size in the pore channels and significantly increase the drug dissolution rate. The insoluble drug, cilostazol, was chosen as a model drug to be loaded into SNT and we developed a simple and efficient method for regulating the drug release by using a gelatin coating with different thicknesses around the SNT. The release rate was adjusted by the amount of gelatin surrounding the SNT, with an increased barrier leading to a reduction in the release rate. A model developed on the basis of the Weibull modulus was established to fit the release results.

  5. Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection

    PubMed Central

    Bear, Joseph C.; Patrick, P. Stephen; Casson, Alfred; Southern, Paul; Lin, Fang-Yu; Powell, Michael J.; Pankhurst, Quentin A.; Kalber, Tammy; Lythgoe, Mark; Parkin, Ivan P.; Mayes, Andrew G.

    2016-01-01

    Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine. PMID:27671546

  6. Ofloxacin Loaded Electrospun Fibers for Ocular Drug Delivery: Effect of Formulation Variables on Fiber Morphology and Drug Release.

    PubMed

    Karataş, Ayşegül; Algan, Aslihan Hilal; Pekel-Bayramgil, Nursel; Turhan, Fatih; Altanlar, Nurten

    2016-01-01

    Ofloxacin (OFL) loaded poly(ε-caprolactone) (PCL) and PCL: poly(butylene succinate) PBS fibers as a drug delivery system in the treatment of ocular infections were prepared by electrospinning. In particular, the effect of some formulation variables including polymer:drug ratio (9:1, 8:2 and 7:3 w/w), solvent systems like dichloromethane (DCM), N,N-dimethylformamide (DMF), N,Ndimethylacetamide (DMAc) and dimethylsulfoxide (DMSO), polymer blends of PCL:PBS at 80:20, 60:40 and 40:60 ratios on fiber morphology, fiber size were investigated. The morphology and diameter of the electrospun fibers were investigated by scanning electron microscopy (SEM) images also the thermal properties were evaluated by differential scanning calorimetry (DSC). The drug release behaviour from fibers and in vitro antibacterial activity were also studied. It was noticed that the average fiber diameter decreased with decreasing polymer amount in initial composition meanwhile the release of drug increased with increasing amount of drug in formulations. Solvent system of DCM:DMF at 80:20 ratio improved fiber morphology and resulted in a reduction in fiber diameter. It was found that smooth surface, flexible fibers with uniform morphology were obtained with 80:20 ratio of PCL:PBS compositions. All fibers showed a burst release of OFL. The initial amount of the released OFL was found to vary as a function of PCL:OFL ratio and polymer composition in the fiber. The microbiological activity of optimized formulation was evaluated using P. aeruginosa, S. epidermidis, S. Aureus and E. coli strains and the results of this study clearly demonstrated that freely released OFL from fibers inhibited the growth of the tested bacteria. The process of electrospinning had no adverse effect on the activity of incorporated drug in fibers.

  7. The impact of preparation parameters on typical attributes of chitosan-heparin nanohydrogels: particle size, loading efficiency, and drug release.

    PubMed

    Shahbazi, Mohammad-Ali; Hamidi, Mehrdad

    2013-11-01

    Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63 ± 0.57 and 75.19 ± 2.65, respectively, when chitosan concentration was 0.75 mg/ml. Besides, heparin addition time of 3 min leaded to 74.1 ± 0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63 ± 1.87, maximum LE of 73.81 ± 3.13 and the slowest drug release with 63.71 ± 3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63 ± 0 and 74.21 ± 1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500 rpm resulted in constant enhancement of LE from 58.3 ± 3.6 to 74.4 ± 2.59 as well as remarkable decrease in size from 148 ± 4.88 to 63 ± 2.64.

  8. Magnetically Vectored Nanocapsules for Tumor Penetration and Remotely Switchable On-Demand Drug Release

    NASA Astrophysics Data System (ADS)

    Kong, Seong Deok

    Hollow-sphere nanocapsules containing intentionally trapped magnetic nanoparticles and defined anticancer drugs provide a powerful magnetic vector under moderate gradient magnetic fields, and enable the nanocapsules to penetrate into the midst of tumors and allow a controlled on-off switchable release of the anticancer drug cargo by remotely applied Radio Frequency (RF) magnetic field. This imageable smart drug delivery system is compact because the drug molecules and magnetic nanoparticles can all be self-contained within 80~150 nm capsules. In vitro as well as in vivo results indicate that the nanocapsules are effective in reducing tumor cell growth. In Chapter 1, the concept of Drug Delivery Systems (DDSs) and the impact of nanotechnology on Drug Delivery Systems were introduced. Triggered drug release using magnetothermally-responsive nanomaterials, magnetic nanoparticles for nanomedicine, and ordered mesoporous materials in the context of Drug Delivery System were discussed. In Chapter 2, creation of remotely controllable, On-Off switchable drug release methodology was described. In this thesis work, triggerable nanocapsules which contain magnetic nanoparticles responsive to external radio frequency (RF) magnetic field have been successfully created. This is in contrast to the regular hollow nanospheres for slow passive release of drugs. The new nanocapsule material consists of bio-inert, bio-compatible or bio-degradable material that we can be selected from a variety of materials depending on specific medical applications. In Chapter 3, study and utilization of magnetic vector for guided tumor penetration was discussed. In the presence of a moderate gradient magnetic field, a powerful magnetic vector is created that allows these nanocapsules to cross cell membranes or blood-tissue barriers and penetrate into the midst of tumors, thus overcoming the well-known problem of limited access of anti-cancer drugs to cancer cells in the interior of a tumor tissue. In

  9. Fabrication of magnetic nanoparticles with controllable drug loading and release through a simple assembly approach.

    PubMed

    Fang, Chen; Kievit, Forrest M; Veiseh, Omid; Stephen, Zachary R; Wang, Tingzhong; Lee, Donghoon; Ellenbogen, Richard G; Zhang, Miqin

    2012-08-20

    Nanoparticle-based cancer therapeutics promises to improve drug delivery safety and efficacy. However, fabrication of consistent theranostic nanoparticles with high and controllable drug loading remains a challenge, primarily due to the cumbersome, multi-step synthesis processes conventionally applied. Here, we present a simple and highly controllable method for assembly of theranostic nanoparticles, which may greatly reduce batch-to-batch variation. The major components of this nanoparticle system include a superparamagnetic iron oxide nanoparticle (SPION), a biodegradable and pH-sensitive poly (beta-amino ester) (PBAE) copolymer, a chemotherapeutic agent doxorubicin (DOX). Here the polymer pre-loaded with drug is directly assembled to the surface of SPIONs forming a drug loaded nanoparticle (NP-DOX). NP-DOX demonstrated a high drug loading efficiency of 679 μg DOX per mg iron, sustained stability in cell culture media up to 7 days, and a strong r(2) relaxivity of 146 mM(-1)•s(-1) for magnetic resonance imaging (MRI). The drug release analysis of NP-DOX showed fast DOX release at pH 5.5 and 6.4 (as in endosomal environment) and slow release at pH 7.4 (physiological condition), demonstrating pH-sensitive drug release kinetics. In vitro evaluation of NP-DOX efficacy using drug-resistant C6 glioma cells showed a 300% increase in cellular internalization at 24h post-treatment and 65% reduction of IC50 at 72 h post-treatment when compared to free DOX. These nanoparticles could serve as a foundation for building smart theranostic formulations for sensitive detection through MRI and effective treatment of cancer by controlled drug release.

  10. Sustained release of Avastin® from polysaccharides cross-linked hydrogels for ocular drug delivery.

    PubMed

    Xu, Xu; Weng, Yuhua; Xu, Lu; Chen, Hao

    2013-09-01

    Avastin(®) was the first choice drug for the treatment of age related macular degeneration (AMD) and proliferative diabetic retinopathy in clinic. Due to its short half-time in intraocular, it was required repeat administration. In this paper, an in situ injectable polysaccharides cross-linked hydrogel was developed for potential ocular drug delivery of avastin. The polysaccharide cross-linked hydrogel was first synthesized by simple mixing of glycol chitosan and oxidized alginate aqueous solution, and then characterized by scanning electron microscopy (SEM) and rheometer. In vitro degradation test indicated that the degradation rate of hydrogels could be controlled by the varying the content of oxidized alginate in hydrogels. In vitro release study showed that the encapsulated avastin had an initial burst release at early stage (within 4 h) followed by a sustained release manner in period of 3 days. With the increase of oxidized alginate concentration in the hydrogel, the release rate of avastin from hydrogels declined accordingly. Meanwhile, the structure stability of avastin released from hydrogels at specific time intervals did not show apparent changes as compared with native avastin based on the analysis of SDS-polyacrylamide gel electrophoresis (SDS-PAEG). As a result, the developed in situ injectable polysaccharides cross-linked hydrogel with controllable degradation rate and drug release might be a versatile carrier for avastin to apply in ocular drug delivery.

  11. Preparation and evaluation of sustained drug release from pluronic polyol rectal suppositories.

    PubMed

    Anderson, D; Amomo, M M

    2001-01-01

    Suppository dosage forms offer several advantages in drug delivery and can be compounded in a pharmacy setting for the needs of the individual patient. In this study, we have examined the use of Pluronic polyols in the development of sustained-release rectal suppository formulations. Solid and liquid Pluronic poyols (Pluronic L61, F68, L101, and F108) were combined in a weight ratio ranging from 80:20 (solid to liquid) to 70:30 to prepare the bases. The release behavior of a model drug, riboflavin, from the suppositories wee evaluated by means of the United Stated Pharmacopeia Basket Dissolution Method. When compared with the control Polybase suppository, which released 50% of the drug (t50) in about 7.23 minutes, Pluronic F68/L61 suppositories at an 80:20 weight ratio exhibited a t50 of 86.5 minutes (1.44 hours). Riboflavin release from suppositories made with Pluronic F108/L101 was even further delayed. The t50 of riboflavin from Pluronic F108/L101 suppositories at an 80:20 weight ratio, for instance, was 274.4 minutes (4.6 hours). The results of this study show that by choosing specific combinations of Pluronic polyols and weight ratios, compounding pharmacists can prepare sustained-release suppository formulations that can deliver drugs within minutes to hours. This flexibility of compounding sustained-release suppositories is beneficial, especially for the management of chronic pain in cancer patients.

  12. Release of polyphenolic drugs from dynamically bonded layer-by-layer films.

    PubMed

    Zhou, Lin; Chen, Mao; Tian, Lili; Guan, Ying; Zhang, Yongjun

    2013-05-01

    Layer-by-layer (LbL) assembled films have been exploited for surface-mediated drug delivery. The drugs loaded in the films were usually released via diffusion or the degradation of one of the film components. Here we demonstrate that drug release can also be achieved by exploiting the dynamic nature of hydrogen-bonded LbL films. The films were fabricated from tannic acid (TA), a model polyphenolic drug, and poly(vinyl pyrrolidone) (PVPON). The driving force for the film buildup is the hydrogen bonding between the two components, which was confirmed by Fourier transform infrared (FTIR) spectra. The film growth is linear, and the growth rate of the film decreases with increasing assembly temperature. Because of the reversible/dynamic nature of hydrogen bonding, when soaked in aqueous solutions, the PVPON/TA films disassemble gradually and thus release TA to the media. The release rate of TA increases with increasing pH and temperature but decreases with increasing ionic strength. Scanning electron microscopy (SEM) studies on the surface morphology of the film during TA release reveal that the film surface becomes smoother and then rougher again because of the dewetting of the film. The released TA can scavenge ABTS(+•) cation radicals, indicating it retains its antioxidant activity, a major biological activity of polyphenols.

  13. Synthesis of CaTiO3 Nanofibers with Controllable Drug-Release Kinetics

    PubMed Central

    Zhang, Qiuhong; Ren, Zhaohui

    2016-01-01

    Calcium titanate (CaTiO3) nanofibers with controlled microstructure were fabricated by a combination of sol–gel and electrospinning approaches. The fiber morphology has been found to rely significantly on the precursor composition. Altering the volume ratio of ethanol to acetic acid from 3.5 to 1.25 enables the morphology of the CaTiO3 nanofibers to be transformed from fibers with a circular cross section to curved ribbon-like structures. Ibuprofen (IBU) was used as a model drug to investigate the drug-loading capacity and drug-release profile of the nanofibers. It was found that the BET surface area and the pore volume decrease markedly with the utilization of F127 surfactant. The nanofibers synthesized without F127 surfactant present the highest drug-loading capacity and the most sustained release kinetics. This study suggests that calcium titanate nanofibers can offer a promising platform for localized drug delivery. PMID:27818612

  14. Alginate-based bipolymeric-nanobioceramic composite matrices for sustained drug release.

    PubMed

    Hasnain, M Saquib; Nayak, Amit Kumar; Singh, Mukul; Tabish, Mohammad; Ansari, Mohammed Tahir; Ara, Tahseen Jahan

    2016-02-01

    Alginate-based bipolymeric-nanobioceramic composite matrices for sustained drug release were developed through incorporation of nano-hydroxyapatite [nHAp] powders within ionotropically-gelled calcium ion-induced alginate-poly (vinyl pyrrolidone) blends polymeric systems. nHAp powders were synthesized by precipitation technique using calcium hydroxide [Ca(OH)2] and orthophosphoric acid [H3PO4] as raw materials. The average particle size of these was synthesized. nHAp powders was found as 19.04 nm and used to prepare nHAp-alginate-PVP beads containing DS. These beads exhibited drug entrapment efficiency (%) of 65.82±1.88 to 94.45±3.72% and average bead sizes of 0.98±0.07 to 1.23±0.15 mm. These beads were characterized by scanning electron microscopy (SEM) and Fourier transform-infra red (FTIR) spectroscopy analyses. Various nHAp-alginate-PVP beads containing DS exhibited prolonged sustained drug release and followed the Koresmeyer-Peppas model of drug release (R2=0.9908-0.9978) with non-Fickian release (anomalous transport) mechanism (n=0.73-0.84) for drug release over 8 h.

  15. Preparation of poly(N-isopropylacrylamide) emulsion gels and their drug release behaviors.

    PubMed

    Tokuyama, Hideaki; Kato, Yuya

    2008-11-15

    Stimuli-sensitive drug delivery systems (DDSs) have attracted considerable attention in medical and pharmaceutical fields; thermosensitive DDS dealing with poly(N-isopropylacrylamide) (poly(NIPA)) have been widely studied. Novel NIPA emulsion gels, i.e., NIPA hydrogels containing distributed oil (oleyl alcohol) microdroplets, were synthesized by means of an emulsion-gelation method in which the polymerization of hydrogels in an aqueous phase in an oil-in-water (O/W) emulsion and the loading of a lipophilic drug (indomethacin) dissolved in an oil phase were accomplished simultaneously. The pulsatile (on-off) drug release from the NIPA emulsion gel loading indomethacin to a phosphate buffered saline (PBS) solution was successfully controlled by a temperature swing between 25 degrees C (release off) and 40 degrees C (release on). The mechanism of the pulsatile drug release was discussed in relation to the diffusion rate, distribution ratio, solvent exchange of NIPA hydrogels, and drug release from an NIPA organogel. The mechanism was as follows: the solvent exchange occurred within the NIPA emulsion gel (the NIPA gel-network absorbed oleyl alcohol with indomethacin) at temperatures above the LCST, and the diffusion rate of indomethacin through the solvent-exchanged gel was higher at 40 degrees C than at 25 degrees C.

  16. Comparison of ionic and non-ionic drug release from multi-membrane spherical aerogels.

    PubMed

    Veronovski, Anja; Knez, Zeljko; Novak, Zoran

    2013-09-15

    The presented research was oriented towards the preparation of dry biodegradable alginate aerogels with multi-membranes using a multi-step sol-gel process with potential applications as carriers during oral drug delivery. First alginate spherical hydrogels were formed in CaCl2 or BaCl2 solutions by ionic cross-linking. These cores were further immersed into alginate sodium solution, filtered through a sieve, and dropped into the salt solution again. Multi-membrane hydrogels were obtained by repeating the above process. They were further converted into aerogels by supercritical drying. The effect of the number of membranes was investigated regarding the loading and release of the model drugs nicotinic acid and theophylline. Moreover, the efficiencies of Ba(2+) and Ca(2+) metal ions for forming tridimensional networks that retain and extend drug release were also investigated. Nicotinic acid release was prolonged by adding membranes around the core and using Ca(2+) for cross-linking. However, retarded theophylline release was only obtained by using Ba(2+) for cross-linking. Namely, by increasing the number of membranes and BaCl2 concentration drug release became linear versus time in all studied cases. In the case of nicotinic acid loading increased by adding membranes around the core, however, for theophylline the opposite results were obtained due to the different nature of the model drugs.

  17. Influence of drug distribution and solubility on release from geopolymer pellets--a finite element method study.

    PubMed

    Jämstorp, Erik; Strømme, Maria; Bredenberg, Susanne

    2012-05-01

    This study investigates the influence of drug solubility and distribution on its release from inert geopolymer pellets of three different sizes (1.5 × 1.5, 3 × 6, and 6 × 6 mm), having the same geopolymer composition and containing highly potent opioid fentanyl, sumatriptan, theophylline, or saccharin. Scanning electron microscopy, nitrogen sorption, drug solubility, permeation, and release experiments were performed, and estimates of the drug diffusion coefficients and solubilities in the geopolymer matrix were derived with the aid of finite element method (FEM). FEM was further employed to investigate the effect of a nonuniform drug distribution on the drug release profile. When inspecting the release profiles for each drug, it was observed that their solubilities in the geopolymer matrix imposed a much greater influence on the drug release rate than their diffusion coefficients. Concentrating the initial drug load in FEM into nonuniformly distributed drug regions inside the matrix created drug release profiles that more closely resembled experimental data than an FEM-simulated uniform drug distribution did. The presented FEM simulations and visualization of drug release from geopolymers under varying initial and dynamic conditions should open up for more systematic studies of additional factors that influence the drug release profile from porous delivery vehicles.

  18. Melt-processed polymeric cellular dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2015-12-28

    The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.

  19. Photothermally activated drug release from liposomes coupled to hollow gold nanoshells

    NASA Astrophysics Data System (ADS)

    Forbes, Natalie; Zasadzinski, Joseph A.

    2011-03-01

    Liposomes show great promise as intravenous drug delivery vehicles, but it is difficult to combine stability in the circulation, extended drug retention and rapid, targeted release at the site of interest. Accessorizing conventional and multicompartment liposomes with photo-activated hollow gold nanoshells (HGN) provides a convenient method to initiate drug release with spatial and temporal control. HGN efficiently absorb near infrared (NIR) light and rapidly convert the absorbed optical energy into heat. Femto- to nano-second NIR light pulses cause the HGNs to rapidly heat, creating large temperature gradients between the HGNs and surrounding fluid. The formation and collapse of unstable vapor bubbles transiently rupture liposome and other bilayer membranes to trigger contents release. Near-complete contents release occurs when the nanoshells are encapsulated within the liposome or tethered to the outer surface of the liposome, with no chemical damage to the contents. Release is achieved by focusing the laser beam at the target, eliminating the need for highly specific targeting ligands or antibodies. Although HGN heating can be intense, the overall energy input is small causing minimal heating of the surroundings. To ensure that drugs are retained within the liposomes until delivery in a physiological environment, we have made novel multicompartment carriers called vesosomes, which consist of an outer lipid bilayer shell that encloses and protects the drug-carrying liposomes. The second bilayer increases the serum half-life of ciprofloxacin from <10 minutes in liposomes to 6 hours in vesosomes and alters the release kinetics. The enhanced drug retention is due to the outer membrane preventing enzymes and proteins in the blood from breaking down the drug-carrying interior compartments.

  20. Controlled release formulations of risperidone antipsychotic drug in novel aliphatic polyester carriers: Data analysis and modelling.

    PubMed

    Siafaka, Panoraia I; Barmpalexis, Panagiotis; Lazaridou, Maria; Papageorgiou, George Z; Koutris, Efthimios; Karavas, Evangelos; Kostoglou, Margaritis; Bikiaris, Dimitrios N

    2015-08-01

    In the present study a series of biodegradable and biocompatible poly(ε-caprolactone)/poly(propylene glutarate) (PCL/PPGlu) polymer blends were investigated as controlled release carriers of Risperidone drug (RISP), appropriate for transdermal drug delivery. The PCL/PPGlu carriers were prepared in different weight ratios. Miscibility studies of blends were evaluated through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolysis studies were performed at 37°C using a phosphate buffered saline solution. The prepared blends have been used for the preparation of RISP patches via solvent evaporation method, containing 5, 10 and 15wt% RISP. These formulations were characterized using FT-IR spectroscopy, DSC and WAXD in order to evaluate interactions taking place between polymer matrix and drug, as well as the dispersion and the physical state of the drug inside the polymer matrix. In vitro drug release studies were performed using as dissolution medium phosphate buffered saline simulating body fluids. It was found that in all cases controlled release formulations were obtained, while the RISP release varies due to the properties of the used polymer blend and the different levels of drug loading. Artificial Neural Networks (ANNs) were used for dissolution behaviour modelling showing increased correlation efficacy compared to Multi-Linear-Regression (MLR).

  1. Natural Non-Mulberry Silk Nanoparticles for Potential-Controlled Drug Release

    PubMed Central

    Wang, Juan; Yin, Zhuping; Xue, Xiang; Kundu, Subhas C.; Mo, Xiumei; Lu, Shenzhou

    2016-01-01

    Natural silk protein nanoparticles are a promising biomaterial for drug delivery due to their pleiotropic properties, including biocompatibility, high bioavailability, and biodegradability. Chinese oak tasar Antheraea pernyi silk fibroin (ApF) nanoparticles are easily obtained using cations as reagents under mild conditions. The mild conditions are potentially advantageous for the encapsulation of sensitive drugs and therapeutic molecules. In the present study, silk fibroin protein nanoparticles are loaded with differently-charged small-molecule drugs, such as doxorubicin hydrochloride, ibuprofen, and ibuprofen-Na, by simple absorption based on electrostatic interactions. The structure, morphology and biocompatibility of the silk nanoparticles in vitro are investigated. In vitro release of the drugs from the nanoparticles depends on charge-charge interactions between the drugs and the nanoparticles. The release behavior of the compounds from the nanoparticles demonstrates that positively-charged molecules are released in a more prolonged or sustained manner. Cell viability studies with L929 demonstrated that the ApF nanoparticles significantly promoted cell growth. The results suggest that Chinese oak tasar Antheraea pernyi silk fibroin nanoparticles can be used as an alternative matrix for drug carrying and controlled release in diverse biomedical applications. PMID:27916946

  2. Oil and drug control the release rate from lyotropic liquid crystals.

    PubMed

    Martiel, Isabelle; Baumann, Nicole; Vallooran, Jijo J; Bergfreund, Jotam; Sagalowicz, Laurent; Mezzenga, Raffaele

    2015-04-28

    The control of the diffusion coefficient by the dimensionality d of the structure appears as a most promising lever to efficiently tune the release rate from lyotropic liquid crystalline (LLC) phases and dispersed particles towards sustained, controlled and targeted release. By using phosphatidylcholine (PC)- and monolinoleine (MLO)-based mesophases with various apolar structural modifiers and water-soluble drugs, we present a comprehensive study of the dimensional structural control of hydrophilic drug release, including 3-d bicontinuous cubic, 2-d lamellar, 1-d hexagonal and 0-d micellar cubic phases in excess water. We investigate how the surfactant, the oil properties and the drug hydrophilicity mitigate or even cancel the effect of structure variation on the drug release rate. Unexpectedly, the observed behavior cannot be fully explained by the thermodynamic partition of the drug into the lipid matrix, which points out to previously overlooked kinetic effects. We therefore interpret our results by discussing the mechanism of structural control of the diffusion rate in terms of drug permeation through the lipid membrane, which includes exchange kinetics. A wide range of implications follow regarding formulation and future developments, both for dispersed LLC delivery systems and topical applications in bulk phase.

  3. Bioerodable PLGA-Based Microparticles for Producing Sustained-Release Drug Formulations and Strategies for Improving Drug Loading

    PubMed Central

    Han, Felicity Y.; Thurecht, Kristofer J.; Whittaker, Andrew K.; Smith, Maree T.

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) is the most widely used biomaterial for microencapsulation and prolonged delivery of therapeutic drugs, proteins and antigens. PLGA has excellent biodegradability and biocompatibility and is generally recognized as safe by international regulatory agencies including the United States Food and Drug Administration and the European Medicines Agency. The physicochemical properties of PLGA may be varied systematically by changing the ratio of lactic acid to glycolic acid. This in turn alters the release rate of microencapsulated therapeutic molecules from PLGA microparticle formulations. The obstacles hindering more widespread use of PLGA for producing sustained-release formulations for clinical use include low drug loading, particularly of hydrophilic small molecules, high initial burst release and/or poor formulation stability. In this review, we address strategies aimed at overcoming these challenges. These include use of low-temperature double-emulsion methods to increase drug-loading by producing PLGA particles with a small volume for the inner water phase and a suitable pH of the external phase. Newer strategies for producing PLGA particles with high drug loading and the desired sustained-release profiles include fabrication of multi-layered microparticles, nanoparticles-in-microparticles, use of hydrogel templates, as well as coaxial electrospray, microfluidics, and supercritical carbon dioxide methods. Another recent strategy with promise for producing particles with well-controlled and reproducible sustained-release profiles involves complexation of PLGA with additives such as polyethylene glycol, poly(ortho esters), chitosan, alginate, caffeic acid, hyaluronic acid, and silicon dioxide. PMID:27445821

  4. Non-polymeric coatings to control drug release from metallic coronary stents

    NASA Astrophysics Data System (ADS)

    Gupta, Celia Edith Macias

    Percutaneous transluminal coronary angiography (PTCA) is a procedure used to re-open narrowed coronary arteries. During PTCA, a coronary stent is expanded inside a diseased vessel and serves as a scaffold to keep the artery open. The major drawback of stenting is restenosis---a re-narrowing of the vessel resulting from the hyperproliferation of smooth muscle cells. Drug eluting stents (DES) reduce the rate of restenosis compared to bare metal stents. Paclitaxel (PAT) is commonly used in DES for its ability to prevent restenosis. However, DES have been associated with thrombosis due to the polymer carrier that controls drug delivery. Therefore, there is a need to change the drug delivery mechanisms to eliminate the need of polymers. The goal of this dissertation is to develop a novel polymer-free drug eluting stent that controls drug release using nanoscale metal coatings. The coating was designed to release PAT as the metal slowly degrades in biological conditions. Once all the Paclitaxel has eluted from the surface, the coating will continue to degrade until the final result is a bare metal stent. The results of this study include a novel non-polymeric drug delivery system using nanoscale coatings that release Paclitaxel at a rate similar to commercial stents, as well as the biocompatibility and efficacy of these coatings. The non-polymeric drug delivery system described here achieved a Paclitaxel release profile equivalent to clinically available Paclitaxel-eluting stents and effectively inhibits smooth muscle cell proliferation, thereby completely eliminating the need for polymers to control drug release from coronary stents.

  5. Evaluating the link between self-assembled mesophase structure and drug release.

    PubMed

    Phan, Stephanie; Fong, Wye-Khay; Kirby, Nigel; Hanley, Tracey; Boyd, Ben J

    2011-12-12

    Lipid-based liquid crystalline materials are of increasing interest for use as drug delivery systems. The intricate nanostructure of the reversed bicontinuous cubic (V(2)) and inverse hexagonal (H(2)) liquid crystal matrices have been shown to provide diffusion controlled release of actives of varying size and polarity. In this study, we extend the understanding of release to other self-assembled phases, the micellar cubic phase (I(2)) and inverse micelles (L(2)). The systems are comparable as they were all prepared from the one lipid, glyceryl monooleate (GMO), which sequentially forms all four phases with increasing hexadecane (HD) content in excess water. Phase identity was confirmed by small angle X-ray scattering (SAXS). SAXS data indicated that four mesophases were formed with increasing HD content at 25°C: V(2) phase (Pn3m space group) formed at 0-4% (w/w) HD, H(2) phase formed at 4-25% (w/w) HD, I(2) phase (Fd3m space group) formed at 25-40% (w/w) HD and finally L(2) phase formed at >40% (w/w) HD. Analogous compositions using phytantriol rather than GMO as the core lipid did not produce the I(2) phase, with only V(2) to H(2) to L(2) transitions being apparent with increasing HD concentration. In order to relate the liquid crystal phase structure to drug release rate, in vitro release tests were conducted by incorporating radio-labelled glucose as a model hydrophilic drug into the four GMO-based mesophases. It was found that the drug release followed first-order diffusion kinetics and was fastest from V(2) followed by L(2), H(2), and I(2). Drug release was shown to be significantly faster from bicontinuous cubic phase than the other mesophases, indicating that the state of the water compartments, whether open or closed, has a great influence on the rate of drug release. It is envisioned that liquid crystalline mesophases with slower release characteristics will more likely have potential applications as sustained release drug delivery systems, and hence

  6. Huperzine A-phospholipid complex-loaded biodegradable thermosensitive polymer gel for controlled drug release.

    PubMed

    Cai, Xiaoqing; Luan, Yuxia; Jiang, Yue; Song, Aixin; Shao, Wei; Li, Zhonghao; Zhao, Zhongxi

    2012-08-20

    The huperzine A-phospholipid complex loaded biodegradable thermosensitive PLGA-PEG-PLGA polymer gel was studied as injectable implant system for controlled release of huperzine-A (HA). First, HA molecules were successfully incorporated into the soybean phosphatidylcholine (SP) molecules to form the huperzine-A-soybean phosphatidylcholine complexes (HA-SPC), which was proved by FT-IR, DSC, XRD, solubility study, TEM, etc. The results indicated that hydrogen bonds and electrostatic interaction between HA and SP molecules play an important role in the formation of HA-SPC. Secondly, the HA-SPC was loaded into biodegradable PLGA-PEG-PLGA thermosensitive gel as injectable implant material to control the release of HA. The in vitro and in vivo drug release behaviors of the prepared products were studied. The in vitro release studies demonstrated that the HA-SPC-loaded gel significantly reduced the initial burst of drug release and extended the release period to about 2 weeks. The in vivo pharmacokinetics study of HA-SPC-loaded gel in rabbits showed that plasma concentration of HA (2.54-0.15ng/mL) was detected for nearly 2 weeks from delivery systems upon single subcutaneous injection. What's more, the in vitro release pattern correlated well with the in vivo pharmacokinetics profile. The present study indicates that HA-SPC loaded PLGA-PEG-PLGA thermal gel may be an attractive candidate vehicle for controlled HA release.

  7. Mechanism of drug release from silica-gelatin aerogel-Relationship between matrix structure and release kinetics.

    PubMed

    Veres, Péter; Kéri, Mónika; Bányai, István; Lázár, István; Fábián, István; Domingo, Concepción; Kalmár, József

    2017-04-01

    Specific features of a silica-gelatin aerogel (3 wt.% gelatin content) in relation to drug delivery has been studied. It was confirmed that the release of both ibuprofen (IBU) and ketoprofen (KET) is about tenfold faster from loaded silica-gelatin aerogel than from pure silica aerogel, although the two matrices are structurally very similar. The main goal of the study was to understand the mechanistic background of the striking difference between the delivery properties of these closely related porous materials. Hydrated and dispersed silica-gelatin aerogel has been characterized by NMR cryoporometry, diffusiometry and relaxometry. The pore structure of the silica aerogel remains intact when it disintegrates in water. In contrast, dispersed silica-gelatin aerogel develops a strong hydration sphere, which reshapes the pore walls and deforms the pore structure. The drug release kinetics was studied on a few minutes time scale with 1s time resolution. Simultaneous evaluation of all relevant kinetic and structural information confirmed that strong hydration of the silica-gelatin skeleton facilitates the rapid desorption and dissolution of the drugs from the loaded aerogel. Such a driving force is not operative in pure silica aerogels.

  8. Degradation and drug release in calcium polyphosphate bioceramics: an MRI-based characterization.

    PubMed

    Bray, J M; Filiaggi, M J; Bowen, C V; Beyea, S D

    2012-10-01

    Degradable, bioceramic bone implants made of calcium polyphosphate (CPP) hold potential for controlled release of therapeutic agents in the treatment of localized bone disease. Magnetic resonance imaging techniques for non-invasively mapping fluid distribution, T(1) and T(2) relaxation times and the apparent diffusion coefficient were performed in conjunction with a drug elution protocol to resolve free and bound water components within the material microstructure in two CPP formulations (G1 and G2). The T(2) maps provided the most accurate estimates of free and bound water, and showed that G1 disks contained a detectable free water component at all times, with drug release dominated by a Fickian diffusion mechanism. Drug release from G2 disks was characterized by a combined diffusional/structural relaxation mechanism, which may be related to the gradual infiltration of a free water component associated with swelling and/or chemical degradation.

  9. Diffusion and Controlled Localized Drug Release from an Injectable Solid Self-Assembling Peptide Hydrogel

    NASA Astrophysics Data System (ADS)

    Sun, Jessie E. P.; Stewart, Brandon; Langhans, Sigrid; Stewart, Joel P.; Pochan, Darrin J.

    2014-03-01

    We use an injectable solid peptide hydrogel (first assembled into a solid hydrogel, can shear-thin flow and immediately reheal on cessation of shear) as a drug delivery vehicle for sustained and active drug release. The triggered intramolecular peptide folding into a beta-hairpin leads to intermolecular assmebly of the peptides into the entangled and branched nanofibrillar hydrogel network responsible for its advantageous rheological properties. The hydrogel is used to encapsulate a highly effective chemotherapeutic, vincristine, with hydrophobic behavior. We show that we are able to constantly maintain drug release in low but still potent concentrations after the shear-thinning injection process. Similarly, the mechanical and morphoogical properties of the gels remains identical after injection. Characterization of the hydrogel construct is through tritiated vincristine release, TEM, confocal microscopy, and in vitro methods.

  10. Polyelectrolyte/carbon nanotube composite microcapsules and drug release triggered by laser irradiation

    NASA Astrophysics Data System (ADS)

    Saito, Haruyuki; Kato, Noritaka

    2016-03-01

    The fabrication of stimuli-responsive capsules is one of the hot topics in the research field of drug delivery systems. Near-infrared (NIR) light is one of the promising stimuli, because of its high transparency to biological tissues, and NIR-responsive capsules have been fabricated using various NIR-adsorbing materials. Here, we employed single-walled carbon nanotubes (SWCNTs) as the NIR-adsorbing material, and microcapsules containing SWCNTs were fabricated by a combination of the layer-by-layer and template-assisted methods. The anti-cancer drug was loaded into the capsules, and the release rates in the dark and under NIR laser irradiation were compared. Distinct release was confirmed in the latter case, whereas almost no release was detected in the former case, indicating that the SWCNT molecule is a suitable light absorber for use with optically addressable drug carriers.

  11. Modeling of drug release from matrix systems involving moving boundaries: approximate analytical solutions.

    PubMed

    Lee, Ping I

    2011-10-10

    The purpose of this review is to provide an overview of approximate analytical solutions to the general moving boundary diffusion problems encountered during the release of a dispersed drug from matrix systems. Starting from the theoretical basis of the Higuchi equation and its subsequent improvement and refinement, available approximate analytical solutions for the more complicated cases involving heterogeneous matrix, boundary layer effect, finite release medium, surface erosion, and finite dissolution rate are also discussed. Among various modeling approaches, the pseudo-steady state assumption employed in deriving the Higuchi equation and related approximate analytical solutions appears to yield reasonably accurate results in describing the early stage release of a dispersed drug from matrices of different geometries whenever the initial drug loading (A) is much larger than the drug solubility (C(s)) in the matrix (or A≫C(s)). However, when the drug loading is not in great excess of the drug solubility (i.e. low A/C(s) values) or when the drug loading approaches the drug solubility (A→C(s)) which occurs often with drugs of high aqueous solubility, approximate analytical solutions based on the pseudo-steady state assumption tend to fail, with the Higuchi equation for planar geometry exhibiting a 11.38% error as compared with the exact solution. In contrast, approximate analytical solutions to this problem without making the pseudo-steady state assumption, based on either the double-integration refinement of the heat balance integral method or the direct simplification of available exact analytical solutions, show close agreement with the exact solutions in different geometries, particularly in the case of low A/C(s) values or drug loading approaching the drug solubility (A→C(s)). However, the double-integration heat balance integral approach is generally more useful in obtaining approximate analytical solutions especially when exact solutions are not

  12. Preparation of alginate hydrogels through solution extrusion and the release behavior of different drugs.

    PubMed

    Liu, Guiting; Zhou, Hongxun; Wu, Hong; Chen, Rong; Guo, Shaoyun

    2016-10-07

    Homogeneous alginate hydrogels were facilely fabricated through solution extrusion process. CaCO3 and D-glucono-δ-lactone (GDL) were used as the gelation agents. The slow gelation of alginate was realized by the in-situ release of Ca(2+) from CaCO3 particles induced by hydrolysis of GDL to reduce pH. Slight gelation during the extrusion caused the enhanced strength of the alginate solutions, leading to the extrudability of the blends. This method enables to produce alginate hydrogels in a single step via extrusion, which is economically advantageous to conventional lab-scale preparation for mass production. Three different drugs, ibuprofen, acetaminophen, and methylthionine chloride, were used as model drugs to evaluate the drug release behavior of the alginate hydrogels. It was demonstrated that the drug release behavior was significantly adjusted by both the drug solubility and the ionic interaction between alginate and the drug molecule. It was shown that solution extrusion process is a feasible method to produce alginate-based drug delivery systems.

  13. TiO2 nanotubes as animal drug delivery system and in vitro controlled release.

    PubMed

    Lai, Shuting; Zhang, Wei; Liu, Fang; Wu, Cui; Zeng, Dongping; Sun, Yongxue; Xu, Yuehua; Fang, Yueping; Zhou, Wuyi

    2013-01-01

    The enrofloxacin hydrochloride (Enro), an anti-inflammatory drug for the animals, was loaded on the TNTs through physical absorption due to the high specific surface area and excellent surface activity of the TiO2 nanotubes. The samples were characterized by XRD, BET, TEM, TG and FTIR. The in vitro controlled release behavior at different temperatures was studied in detail. The results showed that the obtained TNTs were uniform and mainly amorphous crystal phase with a diameter of 10-15 nm and a length of 350-400 nm. By investigating the effect of the hydrothermal reaction process of the obtained TiO2 nanotubes and the drug loading frequency on the loading content of Enro drugs, the results indicated that the increasing loading frequency of the drug was available for the drug loading and the maximum loading content of drug reached to 33.28%. Enro-TNTs performed a better release profile at low temperature than at high temperature in PBS solution. The Higuchi square root models are suitable to explain the in vitro drug release behavior of Enro from Enro-TNTs.

  14. Characterization and in vitro drug release studies of a natural polysaccharide Terminalia catappa gum (Badam gum).

    PubMed

    Meka, Venkata Srikanth; Nali, Sreenivasa Rao; Songa, Ambedkar Sunil; Kolapalli, Venkata Ramana Murthy

    2012-12-01

    The main objective of the present study is the physicochemical characterization of naturally available Terminalia catappa gum (Badam gum [BG]) as a novel pharmaceutical excipient and its suitability in the development of gastroretentive floating drug delivery systems (GRFDDS) to retard the drug for 12 h when the dosage form is exposed to gastrointestinal fluids in the gastric environment. As BG was being explored for the first time for its pharmaceutical application, physicochemical, microbiological, rheological, and stability studies were carried out on this gum. In the present investigation, the physicochemical properties, such as micromeritic, rheological, melting point, moisture content, pH, swelling index, water absorption, and volatile acidity, were evaluated. The gum was characterized by scanning electron microscopy, differential scanning calorimetry (DSC), powder X-ray diffraction studies (PXRD), and Fourier transform infrared spectroscopy (FTIR). Gastroretentive floating tablets of BG were prepared with the model drug propranolol HCl by direct compression methods. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, in vitro drug release, and rate order kinetics. PBG 04 was selected as an optimized formulation based on its 12-h drug release and good buoyancy characteristics. The optimized formulation was characterized with FTIR, DSC, and PXRD studies, and no interaction between the drug and BG was found. Thus, the study confirmed that BG might be used in the gastroretentive drug delivery system as a release-retarding polymer.

  15. Controllable biodegradability, drug release behavior and hemocompatibility of PTX-eluting magnesium stents.

    PubMed

    Lu, Ping; Fan, Hainan; Liu, Yin; Cao, Lu; Wu, Xiangfeng; Xu, Xinhua

    2011-03-01

    Cardiovascular magnesium-based stents have been already applied in patients. However, their high corrosion rate hinders their clinical application. In this study, we adopt a new approach in the design of a Mg-based stent to improve the biodegradation rate and the drug release rate. By fabricating a micro-arc oxidation/poly-l-lactic acid (MAO/PLLA) composite coating on the magnesium alloy AZ81 substrate, the corrosion resistance decreased and the biodegradation rate became controllable. The drug release coating was composed of one Poly(dl-lactide-co-glycolide)/paclitaxel (PLGA/PTX) layer and one pure PLGA blank layer without paclitaxel, and this coating also functions to provide controlled biodegradation rate of the stent. The drug release rate was controlled by controlling the ratio of the LA:GA of the PLGA without PTX. The scanning electron microscopy (SEM) images were used to demonstrate the morphology of the samples before and after this modification. The blood compatibility of the samples was demonstrated by the platelet adhesion test. The drug release was determined by ultraviolet-visible (UV-visible) spectrophotometer. The result showed that the PLLA effectively sealed the micro-cracks and micro-holes on the surface of the MAO coating to give controllable biodegradation of the AZ81. The drug release rate of PTX exhibited a nearly linear sustained-release profile with no significant burst releases that would come from the uncontrolled oxidation/corrosion of AZ81. The samples modified had better hemocompatibility than 316L stainless steel.

  16. Direct encapsulation of water-soluble drug into silica microcapsules for sustained release applications

    SciTech Connect

    Wang Jiexin; Wang Zhihui; Chen Jianfeng Yun, Jimmy

    2008-12-01

    Direct encapsulation of water-soluble drug into silica microcapsules was facilely achieved by a sol-gel process of tetraethoxysilane (TEOS) in W/O emulsion with hydrochloric acid (HCl) aqueous solution containing Tween 80 and drug as well as cyclohexane solution containing Span 80. Two water-soluble drugs of gentamicin sulphate (GS) and salbutamol sulphate (SS) were chosen as model drugs. The characterization of drug encapsulated silica microcapsules by scanning electronic microscopy (SEM), FTIR, thermogravimetry (TG) and N{sub 2} adsorption-desorption analyses indicated that drug was successfully entrapped into silica microcapsules. The as-prepared silica microcapsules were uniform spherical particles with hollow structure, good dispersion and a size of 5-10 {mu}m, and had a specific surface area of about 306 m{sup 2}/g. UV-vis and thermogravimetry (TG) analyses were performed to determine the amount of drug encapsulated in the microcapsules. The BJH pore size distribution (PSD) of silica microcapsules before and after removing drug was examined. In vitro release behavior of drug in simulated body fluid (SBF) revealed that such system exhibited excellent sustained release properties.

  17. Intelligent Janus nanoparticles for intracellular real-time monitoring of dual drug release

    NASA Astrophysics Data System (ADS)

    Cao, Han; Yang, Yuhong; Chen, Xin; Shao, Zhengzhong

    2016-03-01

    Stimuli-responsive nanomaterials have been receiving much attention as drug delivery carriers, however understanding of multi-drug release from the carriers for efficient therapeutics is highly challenging. Here, we report a novel nanosystem, Janus particle Dox-CMR-MS/Au-6MP (Dox: doxorubicin, CMR: 7-hydroxycoumarin-3-carboxylate, MS: mesoporous silica, Au: gold, 6MP: 6-mercaptopurine) with opposing MS and Au faces, which can monitor intracellular dual-drug (Dox and 6MP) controlled release in real time based on fluorescence resonance energy transfer (FRET) and surface-enhanced Raman scattering (SERS). The FRET acceptor Dox is attached to CMR (as a FRET donor) conjugated MS with a pH-responsive linker hydrazone, and 6MP is conjugated to the Au surface through the gold-thiol interaction. As the Janus nanoparticle enters into tumor cells, the breakage of the hydrazone bond in an acidic environment and the substitution of glutathione (GSH) overexpressed in cancer cells give rise to the release of Dox and 6MP, respectively. Thus, the change of the CMR fluorescence signal and the SERS decrease of 6MP can be used to monitor the dual-drug release within living cells in real time. In addition, this work demonstrates the enhanced anticancer effect of the designed dual-drug loaded nanosystem. Therefore, the current study may provide new perspectives for the real-time study of intelligent multi-drug delivery and release, as well as cellular responses to drug treatment.Stimuli-responsive nanomaterials have been receiving much attention as drug delivery carriers, however understanding of multi-drug release from the carriers for efficient therapeutics is highly challenging. Here, we report a novel nanosystem, Janus particle Dox-CMR-MS/Au-6MP (Dox: doxorubicin, CMR: 7-hydroxycoumarin-3-carboxylate, MS: mesoporous silica, Au: gold, 6MP: 6-mercaptopurine) with opposing MS and Au faces, which can monitor intracellular dual-drug (Dox and 6MP) controlled release in real time based on

  18. Photoactive Fluoropolymer Surfaces that Release Sensitizer Drug Molecules

    PubMed Central

    Ghosh, Goutam; Minnis, Mihaela; Ghogare, Ashwini A.; Abramova, Inna; Cengel, Keith; Busch, Theresa M.; Greer, Alexander

    2015-01-01

    We describe a physical-organic study of two fluoropolymers bearing a photoreleasable PEGylated photosensitizer which generates 1O2(1Δg) [chlorin e6 methoxy tri(ethylene glycol) triester]. The surfaces are Teflon/polyvinylalcohol (PVA) nanocomposite and fluorinated silica. The relative efficiency of these surfaces to photorelease the PEGylated sensitizer [shown previously to be phototoxic to ovarian cancer cells (Kimani, S. et al J. Org. Chem 2012, 77, 10638)] was slightly higher for the nanocomposite. In the presence of red light and O2, 1O2 is formed, which cleaves an ethene linkage to liberate the sensitizer in 68–92% yields. The fluoropolymers were designed to deal with multiple problems. Namely, their success relied not only high O2 solubility and drug repellency, but that the C−F bonds physically quench little 1O2 for its productive use away from the surface. The results obtained here indicate that Teflon-like surfaces have potential uses of delivering sensitizer and singlet oxygen for applications in tissue repair and photodynamic therapy (PDT). PMID:25686407

  19. Photoactive fluoropolymer surfaces that release sensitizer drug molecules.

    PubMed

    Ghosh, Goutam; Minnis, Mihaela; Ghogare, Ashwini A; Abramova, Inna; Cengel, Keith A; Busch, Theresa M; Greer, Alexander

    2015-03-12

    We describe a physical-organic study of two fluoropolymers bearing a photoreleasable PEGylated photosensitizer that generates (1)O2((1)Δg) [chlorin e6 methoxy tri(ethylene glycol) triester]. The surfaces are Teflon/poly(vinyl alcohol) (PVA) nanocomposite and fluorinated silica. The relative efficiency of these surfaces to photorelease the PEGylated sensitizer [shown previously to be phototoxic to ovarian cancer cells (Kimani, S. et al. J. Org. Chem 2012, 77, 10638)] was slightly higher for the nanocomposite. In the presence of red light and O2, (1)O2 is formed, which cleaves an ethene linkage to liberate the sensitizer in 68-92% yield. The fluoropolymers were designed to deal with multiple problems. Namely, their success relied not only on high O2 solubility and drug repellency but also on the C-F bonds, which physically quench little (1)O2, for singlet oxygen's productive use away from the surface. The results obtained here indicate that Teflon-like surfaces have potential uses in delivering sensitizer and singlet oxygen for applications in tissue repair and photodynamic therapy (PDT).

  20. Functionalized mesoporous materials for adsorption and release of different drug molecules: A comparative study

    SciTech Connect

    Wang Gang; Otuonye, Amy N.; Blair, Elizabeth A.; Denton, Kelley; Tao Zhimin; Asefa, Tewodros

    2009-07-15

    The adsorption capacity and release properties of mesoporous materials for drug molecules can be improved by functionalizing their surfaces with judiciously chosen organic groups. Functionalized ordered mesoporous materials containing various types of organic groups via a co-condensation synthetic method from 15% organosilane and by post-grafting organosilanes onto a pre-made mesoporous silica were synthesized. Comparative studies of their adsorption and release properties for various model drug molecules were then conducted. Functional groups including 3-aminopropyl, 3-mercaptopropyl, vinyl, and secondary amine groups were used to functionalize the mesoporous materials while rhodamine 6G and ibuprofen were utilized to investigate the materials' relative adsorption and release properties. The self-assembly of the mesoporous materials was carried out in the presence of cetyltrimethylammonium bromide (CTAB) surfactant, which produced MCM-41 type materials with pore diameters of {approx}2.7-3.3 nm and moderate to high surface areas up to {approx}1000 m{sup 2}/g. The different functional groups introduced into the materials dictated their adsorption capacity and release properties. While mercaptopropyl and vinyl functionalized samples showed high adsorption capacity for rhodamine 6G, amine functionalized samples exhibited higher adsorption capacity for ibuprofen. While the diffusional release of ibuprofen was fitted on the Fickian diffusion model, the release of rhodamine 6G followed Super Case-II transport model. - Graphical abstract: The adsorption capacity and release properties of mesoporous materials for various drug molecules are tuned by functionalizing the surfaces of the materials with judiciously chosen organic groups. This work reports comparative studies of the adsorption and release properties of functionalized ordered mesoporous materials containing different hydrophobic and hydrophilic groups that are synthesized via a co-condensation and post

  1. Physicochemical and drug release characteristics of acetylated starches of five Lagenaria siceraria cultivars.

    PubMed

    Kulkarni, Sameer D; Sinha, Barij N; Kumar, K Jayaram

    2015-01-01

    Modified starches play a crucial role in the pharmaceutical industries in controlling the drug release at a pre-determined rate. The effect of acetylation on the physicochemical and drug release characteristics of the starches from five different Indian L. siceraria cultivars was investigated. Starches isolated from the seeds of L. siceraria were subjected to varying degrees of acetylation. Using a range of characterization methods including amylose content, elemental analysis, light transmittance, swelling power, scanning electron microscopy, FT-IR and X-ray diffraction, the effect of acetylation was determined. The swelling power of starch acetates improved significantly (P < 0.05) with the increase in degree of substitution. The increase in swelling shows that acetylation improved the accessibility of an amorphous area to the water. The formation of V-type of complex crystalline structures confirmed the acetylation of L. siceraria starch. Modification in the crystalline structure of starch acetate retarded the drug release, which is controlled by water uptake. The starch acetates from all the cultivars showed better sustained release properties with the increase in degree of substitution. Drug release through the swellable matrix was found to be controlled by fickian diffusion from the gel layer as indicated by Korsmeyer-Peppas models (R(2)) 0.9885-0.9984.

  2. Nanosized sustained-release drug depots fabricated using modified tri-axial electrospinning.

    PubMed

    Yang, Guang-Zhi; Li, Jiao-Jiao; Yu, Deng-Guang; He, Mei-Feng; Yang, Jun-He; Williams, Gareth R

    2017-01-27

    Nanoscale drug depots, comprising a drug reservoir surrounded by a carrier membrane, are much sought after in contemporary pharmaceutical research. Using cellulose acetate (CA) as a filament-forming polymeric matrix and ferulic acid (FA) as a model drug, nanoscale drug depots in the form of core-shell fibers were designed and fabricated using a modified tri-axial electrospinning process. This employed a solvent mixture as the outer working fluid, as a result of which a robust and continuous preparation process could be achieved. The fiber-based depots had a linear morphology, smooth surfaces, and an average diameter of 0.62±0.07μm. Electron microscopy data showed them to have clear core-shell structures, with the FA encapsulated inside a CA shell. X-ray diffraction and IR spectroscopy results verified that FA was present in the crystalline physical form. In vitro dissolution tests revealed that the fibers were able to provide close to zero-order release over 36h, with no initial burst release and minimal tailing-off. The release properties of the depot systems were much improved over monolithic CA/FA fibers, which exhibited a significant burst release and also considerable tailing-off at the end of the release experiment. Here we thus demonstrate the concept of using modified tri-axial electrospinning to design and develop new types of heterogeneous nanoscale biomaterials.

  3. Cyclodextrin modified hydrogels of PVP/PEG for sustained drug release.

    PubMed

    Nielsen, Anne Louise; Madsen, Flemming; Larsen, Kim Lambertsen

    2009-02-01

    Hydrogels are water swollen networks of polymers and especially hydrogels consisting of poly vinylpyrrolidone/poly ethyleneglycol-dimethacrylate (PVP/PEG-DMA) blends show promising wound care properties. Enhanced functionality of the hydrogels can be achieved by incorporating drugs and other substances that may assist wound healing into the gel matrix. Controlling the release of active compounds from the hydrogels may be possible by carefully modifying the polymer matrix. For this purpose, cyclodextrins (CD) were grafted to the polymer matrix in 4-5 w/w% in an attempt to retard the release of water-soluble drugs. Ibuprofenate (IBU) was chosen as model drug and loaded in IBU/CD ratios of 0.6, 1.2, and 2.5. Vinyl derivatives of alpha-, beta- and gamma-CD were produced, added to the prepolymer blend and cured by UV-light. During this curing process the CD derivatives were covalently incorporated into the hydrogel matrix. The modified hydrogels were loaded with ibuprofenate by swelling. The release of the model drug from CD modified hydrogels show that especially covalently bonded beta-cyclodextrin can change both the release rate and the release profile of ibuprofen.

  4. Mimicking Biological Delivery Through Feedback-Controlled Drug Release Systems Based on Molecular Imprinting

    PubMed Central

    Kryscio, David R.; Peppas, Nicholas A.

    2015-01-01

    Intelligent drug delivery systems (DDS) are able to rapidly detect a biological event and respond appropriately by releasing a therapeutic agent; thus, they are advantageous over their conventional counterparts. Molecular imprinting is a promising area that generates a polymeric network which can selectively recognize a desired analyte. This field has been studied for a variety of applications over a long period of time, but only recently has it been investigated for biomedical and pharmaceutical applications. Recent work in the area of molecularly imprinted polymers in drug delivery highlights the potential of these recognitive networks as environmentally responsive DDS that can ultimately lead to feedback controlled recognitive release systems. PMID:26500352

  5. The role of polymer membrane formation in sustained release drug delivery systems.

    PubMed

    McHugh, A J

    2005-12-05

    A discussion of the role of polymer membrane-based drug delivery systems is presented. This is followed with a review of recent studies in our laboratories of the membrane formation and drug delivery characteristics of injectable polymer solution platforms. Attention is focused on the role of depot formulation in terms of solvent quality and water miscibility and polymer type (amorphous versus crystallizable), as well as the effects of bath-side additives on the in vitro release behavior. A quantitative model describing the protein release dynamics in fast phase inverting systems (FPI) is also discussed.

  6. Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose.

    PubMed

    Yi, Tao; Wan, Jiangling; Xu, Huibi; Yang, Xiangliang

    2008-08-07

    The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.

  7. The effect of porosity on drug release kinetics from vancomycin microsphere/calcium phosphate cement composites.

    PubMed

    Schnieders, Julia; Gbureck, Uwe; Vorndran, Elke; Schossig, Michael; Kissel, Thomas

    2011-11-01

    The influence of porosity on release profiles of antibiotics from calcium phosphate composites was investigated to optimize the duration of treatment. We hypothesized, that by the encapsulation of vancomycin-HCl into biodegradable microspheres prior admixing to calcium phosphate bone cement, the influence of porosity of the cement matrix on vancomycin release could be reduced. Encapsulation of vancomycin into a biodegradable poly(lactic co-glycolic acid) copolymer (PLGA) was performed by spray drying; drug-loaded microparticles were added to calcium phosphate cement (CPC) at different powder to liquid ratios (P/L), resulting in different porosities of the cement composites. The effect of differences in P/L ratio on drug release kinetics was compared for both the direct addition of vancomycin-HCl to the cement liquid and for cement composites modified with vancomycin-HCl-loaded microspheres. Scanning electron microscopy (SEM) was used to visualize surface and cross section morphology of the different composites. Brunauer, Emmett, and Teller-plots (BET) was used to determine the specific surface area and pore size distribution of these matrices. It could be clearly shown, that variations in P/L ratio influenced both the porosity of cement and vancomycin release profiles. Antibiotic activity during release study was successfully measured using an agar diffusion assay. However, vancomycin-HCl encapsulation into PLGA polymer microspheres decreased porosity influence of cement on drug release while maintaining antibiotic activity of the embedded substance.

  8. Controlled release drug delivery systems to improve post-operative pharmacotherapy.

    PubMed

    Bhusal, Prabhat; Harrison, Jeff; Sharma, Manisha; Jones, David S; Hill, Andrew G; Svirskis, Darren

    2016-10-01

    Over 230 million surgical procedures are conducted worldwide each year with numbers increasing. Pain, undesirable inflammation and infection are common complications experienced by patients following surgery. Opioids, non-steroidal anti-inflammatory drugs (NSAIDs), local anaesthetics (LAs) and antibiotics are the commonly administered drugs peri-operatively to manage these complications. Post-operative pharmacotherapy is typically achieved using immediate-release dosage forms of drugs, which lead to issues around fluctuating plasma concentrations, systemic adverse effects and poor patient adherence. Controlled release (CR) systems for certain medicines including opioids, NSAIDs and antibiotics have demonstrably enhanced treatment efficacy in the post-surgical setting. However, challenges remain to ensure patient safety while achieving individual therapeutic needs. Newer CR systems in the research and development pipeline have a high level of control over medicine release, which can be initiated, tuned or stopped on-demand. Future systems will self-regulate drug release in response to biological markers providing precise individualized therapy. In this review, we cover currently adopted CR systems in post-operative pharmacotherapy, including drug eluting medical devices, and highlight a series of examples of novel CR technologies that have the potential for translation into post-surgical settings to improve medication efficacy and enhance post-surgical recovery.

  9. A new scleroglucan/borax hydrogel: swelling and drug release studies.

    PubMed

    Coviello, Tommasina; Grassi, Mario; Palleschi, Antonio; Bocchinfuso, Gianfranco; Coluzzi, Gina; Banishoeib, Fateme; Alhaique, Franco

    2005-01-31

    The aim of the work was the characterization of a new polysaccharidic physical hydrogel, obtained from Scleroglucan (Sclg) and borax, following water uptake and dimension variations during the swelling process. Furthermore, the release of molecules of different size (Theophylline (TPH), Vitamin B12 (Vit. B12) and Myoglobin (MGB)) from the gel and from the dried system used as a matrix for tablets was studied. The increase of weight of the tablets with and without the loaded drugs was followed together with the relative variation of the dimensions. The dry matrix, in the form of tablets was capable, during the swelling process, to incorporate a relevant amount of solvent (ca. 20 g water/g dried matrix), without dissolving in the medium, leading to a surprisingly noticeable anisotropic swelling that can be correlated with a peculiar supramolecular structure of the system induced by compression. Obtained results indicate that the new hydrogel can be suitable for sustained drug release formulations. The delivery from the matrix is deeply dependent on the size of the tested model drugs. The experimental release data obtained from the gel were satisfactorily fitted by an appropriate theoretical approach and the relative drug diffusion coefficients in the hydrogel were estimated. The release profiles of TPH, Vit. B12 and MGB from the tablets have been analyzed in terms of a new mathematical approach that allows calculating of permeability values of the loaded drugs.

  10. Doxorubicin loaded nanodiamond-silk spheres for fluorescence tracking and controlled drug release

    PubMed Central

    Khalid, Asma; Mitropoulos, Alexander N.; Marelli, Benedetto; Tomljenovic-Hanic, Snjezana; Omenetto, Fiorenzo G.

    2015-01-01

    Nanoparticle (NP) based technologies have proved to be considerably beneficial for advances in biomedicine especially in the areas of disease detection, drug delivery and bioimaging. Over the last few decades, NPs have garnered interest for their exemplary impacts on the detection, treatment, and prevention of cancer. The full potential of these technologies are yet to be employed for clinical use. The ongoing research and development in this field demands single multifunctional composite materials that can be employed simultaneously for drug delivery and biomedical imaging. In this manuscript, a unique combination of silk fibroin (SF) and nanodiamonds (NDs) in the form of nanospheres are fabricated and investigated. The spheres were loaded with the anthracyline Doxorubicin (DoX) and the drug release kinetics for these ND-SF-DoX (NDSX) spheres were studied. NDs provided the fluorescence modality for imaging while the degradable SF spheres stabilized and released the drug in a controlled manner. The emission and structural properties of the spheres were characterized during drug release. The degradability of SF and the subsequent release of DoX from the spheres were monitored through fluorescence of NDs inside the spheres. This research demonstrates the enormous potential of the ND-SF nanocomposite platforms for diagnostic and therapeutic purposes, which are both important for pharmaceutical research and clinical settings. PMID:26819823

  11. Microwave initiated synthesis of polyacrylamide grafted carboxymethylstarch (CMS-g-PAM): application as a novel matrix for sustained drug release.

    PubMed

    Sen, Gautam; Pal, Sagar

    2009-07-01

    This paper reports the investigation of microwave initiated synthesized polyacrylamide grafted carboxymethylstarch (CMS-g-PAM) as matrix for sustained drug release. 'In vitro' release of a model drug (5-amino salicylic acid) from CMS-g-PAM matrix has been studied. It is evident that higher the percentage grafting, more sustained is the rate of drug release. Further, the percentage grafting vs. t(50) value (i.e. time taken for release of 50% of the enclosed drug) correlation has been successfully studied for the first time. This correlation will lead to the possibility of a programmable drug release matrix based on grafted polysaccharide. In this matrix, the rate of release of the enclosed drug can be precisely programmed simply by adjustment of percentage grafting during synthesis.

  12. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear

    NASA Astrophysics Data System (ADS)

    Yu, Zhan; Yu, Min; Zhang, Zhibao; Hong, Ge; Xiong, Qingqing

    2014-07-01

    Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders.

  13. Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability.

    PubMed

    Gulati, Karan; Kogawa, Masakazu; Prideaux, Matthew; Findlay, David M; Atkins, Gerald J; Losic, Dusan

    2016-12-01

    There is an ongoing demand for new approaches for treating localized bone pathologies. Here we propose a new strategy for treatment of such conditions, via local delivery of hormones/drugs to the trauma site using drug releasing nano-engineered implants. The proposed implants were prepared in the form of small Ti wires/needles with a nano-engineered oxide layer composed of array of titania nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix containing human osteoblast-like, and the results confirmed cell migration onto the implants and their attachment and spread. To investigate therapeutic efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved anabolic therapeutic for the treatment of severe bone fractures, were inserted into 3D gels containing osteoblast-like cells. Gene expression studies revealed a suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH from TNTs at concentrations sufficient to alter cell function. The performance of the TNTs wire implants using an example of a drug needed at relatively higher concentrations, the anti-inflammatory drug indomethacin, is also demonstrated. Finally, the mechanical stability of the prepared implants was tested by their insertion into bovine trabecular bone cores ex vivo followed by retrieval, which confirmed the robustness of the TNT structures. This study provides proof of principle for the suitability of the TNT/Ti wire implants for localized bone therapy, which can be customized to cater for specific therapeutic requirements.

  14. Effects of Particle Hydrophobicity, Surface Charge, Media pH Value and Complexation with Human Serum Albumin on Drug Release Behavior of Mitoxantrone-Loaded Pullulan Nanoparticles

    PubMed Central

    Tao, Xiaojun; Jin, Shu; Wu, Dehong; Ling, Kai; Yuan, Liming; Lin, Pingfa; Xie, Yongchao; Yang, Xiaoping

    2015-01-01

    We prepared two types of cholesterol hydrophobically modified pullulan nanoparticles (CHP) and carboxyethyl hydrophobically modified pullulan nanoparticles (CHCP) substituted with various degrees of cholesterol, including 3.11, 6.03, 6.91 and 3.46 per polymer, and named CHP−3.11, CHP−6.03, CHP−6.91 and CHCP−3.46. Dynamic laser light scattering (DLS) showed that the pullulan nanoparticles were 80–120 nm depending on the degree of cholesterol substitution. The mean size of CHCP nanoparticles was about 160 nm, with zeta potential −19.9 mV, larger than CHP because of the carboxyethyl group. A greater degree of cholesterol substitution conferred greater nanoparticle hydrophobicity. Drug-loading efficiency depended on nanoparticle hydrophobicity, that is, nanoparticles with the greatest degree of cholesterol substitution (6.91) showed the most drug encapsulation efficiency (90.2%). The amount of drug loading increased and that of drug release decreased with enhanced nanoparticle hydrophobicity. Nanoparticle surface-negative charge disturbed the amount of drug loading and drug release, for an opposite effect relative to nanoparticle hydrophobicity. The drug release in pullulan nanoparticles was higher pH 4.0 than pH 6.8 media. However, the changed drug release amount was not larger for negative-surface nanoparticles than CHP nanoparticles in the acid release media. Drug release of pullulan nanoparticles was further slowed with human serum albumin complexation and was little affected by nanoparticle hydrophobicity and surface negative charge. PMID:28344259

  15. Biointerfacing polymeric microcapsules for in vivo near-infrared light-triggered drug release

    NASA Astrophysics Data System (ADS)

    Shao, Jingxin; Xuan, Mingjun; Si, Tieyan; Dai, Luru; He, Qiang

    2015-11-01

    Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid release of encapsulated water-soluble drug. In vivo antitumor tests demonstrate that this microcapsule has the effective ability of inhibiting tumor growth and preventing metastases. Real time in vivo fluorescence imaging results confirm that capsules can be excreted gradually from the animal body which in turn demonstrates the biocompatibility and biodegradation of these biointerfacing GNR-microcapsules. This intelligent system provides a novel anticancer platform with the advantages of controlled release, biological friendliness and credible biosafety.Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid

  16. A poly(ε-caprolactone) device for sustained release of an anti-glaucoma drug.

    PubMed

    Natu, Mădălina V; Gaspar, Manuel N; Ribeiro, Carlos A Fontes; Correia, Ilídio J; Silva, Daniela; de Sousa, Hermínio C; Gil, M H

    2011-04-01

    Implantable dorzolamide-loaded discs were prepared by blending poly(ε-caprolactone), PCL, with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Lu. By blending, crystallinity, water uptake and mass loss were modified relative to the pure polymers. Burst was diminished by coating the discs with a PCL shell. All samples presented burst release except PCL-coated samples that showed controlled release during 18 days. For PCL-coated samples, barrier control of diffusion coupled with partition control from the core slowed down the release, while for 50/50 Lu/PCL-coated samples, the enhancement in the porosity of the core diminished partition control of drug release. Nonlinear regression analysis suggested that a degradation model fully describes the release curve considering a triphasic release mechanism: the instantaneous diffusion (burst), diffusion and polymer degradation stages. The MTT test indicated that the materials are not cytotoxic for corneal endothelial cells. A good in vitro-in vivo correlation was obtained, with similar amounts of drug released in vitro and in vivo. The discs decreased intraocular pressure (IOP) in normotensive rabbit eyes by 13.0% during 10 days for PCL-coated and by 13.0% during 4 days for 50/50 Lu/PCL-coated samples. The percentages of IOP decrease are similar to those obtained by dorzolamide eyedrop instillation (11.0%).

  17. Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets

    PubMed Central

    Jayasree, J.; Sivaneswari, S.; Hemalatha, G.; Preethi, N.; Mounika, B.; Murthy, S. Vasudeva

    2014-01-01

    Objective: The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Materials and Methods: Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results and Discussion: Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer — Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Conclusion: Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability. PMID:25426439

  18. Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

    NASA Astrophysics Data System (ADS)

    Rodzinski, Alexandra; Guduru, Rakesh; Liang, Ping; Hadjikhani, Ali; Stewart, Tiffanie; Stimphil, Emmanuel; Runowicz, Carolyn; Cote, Richard; Altman, Norman; Datar, Ram; Khizroev, Sakhrat

    2016-02-01

    It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane’s electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry.

  19. Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

    PubMed Central

    Rodzinski, Alexandra; Guduru, Rakesh; Liang, Ping; Hadjikhani, Ali; Stewart, Tiffanie; Stimphil, Emmanuel; Runowicz, Carolyn; Cote, Richard; Altman, Norman; Datar, Ram; Khizroev, Sakhrat

    2016-01-01

    It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane’s electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry. PMID:26875783

  20. The affective dimension of pain as a risk factor for drug and alcohol addiction.

    PubMed

    LeBlanc, Dana M; McGinn, M Adrienne; Itoga, Christy A; Edwards, Scott

    2015-12-01

    Addiction, or substance use disorder (SUD), is a devastating psychiatric disease composed of multiple elemental features. As a biobehavioral disorder, escalation of drug and/or alcohol intake is both a cause and consequence of molecular neuroadaptations in central brain reinforcement circuitry. Multiple mesolimbic areas mediate a host of negative affective and motivational symptoms that appear to be central to the addiction process. Brain stress- and reinforcement-related regions such as the central amygdala (CeA), prefrontal cortex (PFC), and nucleus accumbens (NAc) also serve as central processors of ascending nociceptive input. We hypothesize that a sensitization of brain mechanisms underlying the processing of persistent and maladaptive pain contributes to a composite negative affective state to drive the enduring, relapsing nature of addiction, particularly in the case of alcohol and opioid use disorder. At the neurochemical level, pain activates central stress-related neuropeptide signaling, including the dynorphin and corticotropin-releasing factor (CRF) systems, and by this process may facilitate negative affect and escalated drug and alcohol use over time. Importantly, the widespread prevalence of unresolved pain and associated affective dysregulation in clinical populations highlights the need for more effective analgesic medications with reduced potential for tolerance and dependence. The burgeoning epidemic of prescription opioid abuse also demands a closer investigation into the neurobiological mechanisms of how pain treatment could potentially represent a significant risk factor for addiction in vulnerable populations. Finally, the continuing convergence of sensory and affective neuroscience fields is expected to generate insight into the critical balance between pain relief and addiction liability, as well as provide more effective therapeutic strategies for chronic pain and addiction.

  1. Setting radon-specific release criteria and demonstrating compliance for land affected by NORM.

    PubMed

    García-Talavera, M; Martínez, M; Matarranz, J L M; Ramos, L

    2008-11-01

    Residues from industrial activities involving naturally occurring radioactive materials (NORMs) may cause radiation exposures to members of the public, particularly when NORM-affected land is brought into residential use. To provide an adequate protection against radiation in such situations, the following limiting criteria are currently required in Spain for releasing NORM-affected land: (i) no more than a 300 microSv yr(-1) increase (excluding radon doses) over the natural background; (ii) (222)Rn concentrations in hypothetical future dwellings lower than 200 Bq m(-3); and (iii) reduction of all radiation exposures to as low as reasonable achievable. This paper addresses some of the problems encountered in translating the (222)Rn criterion into site-specific release limits and in demonstrating compliance with them.

  2. Engineering hot-melt extruded solid dispersion for controlled release of hydrophilic drugs.

    PubMed

    Zhang, Shuli; Meng, Xuan; Wang, Zheng; Fan, Aiping; Wang, Guocheng; Zhao, Yanjun; Tang, Yu

    2017-03-30

    It is often challenging to precisely manipulate the release behavior of hydrophilic drugs that is believed to be crucial for a satisfactory therapeutic outcome. The aim of this work was to regulate the dissolution of hydrophilic drug from hot-melt extruded solid dispersion via rational screening of the pore-forming agents. Venlafaxine hydrochloride and Compritol® 888 ATO was selected as the model drug and carrier excipient, respectively. Hydrophilic polyethylene glycol (PEG 6000) and polyvinylpyrolidone (PVP K30) were chosen as the transient pore-forming agents. The X-ray diffraction and thermal analysis showed that both drug and carrier existed in the crystalline form. Both types of polymers could generate pores upon dissolution test and the drug release rate was proportionally correlated to the pore-forming agent content. The mathematical modelling showed that the Ritger-Peppas model gave the best fit to the release curves, which demonstrates a diffusion-dominant release mechanism. The scanning electron microscopy and mercury intrusion porosimetry analysis proved that PVP K30 could generate large pores with low porosity, but PEG 6000 produced smaller pores with relatively high porosity. The in vivo pharmacokinetics study in rat revealed that solid dispersions containing either PEG 6000 or PVP K30 (both at 2.5%, w/w) exhibited an elevated bioavailability compared to the commercial product, Effexor® XR. The current work implied that rational screening of transient pore-forming polymer in solid dispersion could be a robust approach for controlling hydrophilic drug release.

  3. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2016-06-01

    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration.

  4. Formulation and characterization of sustained release dosage form of moisture sensitive drug

    PubMed Central

    Patel, Priya; Dave, Abhishek; Vasava, Amit; Patel, Paresh

    2015-01-01

    Objective: The purpose of this study was to prepare sustained release tablet of moisture sensitive drug like Ranitidine Hydrochloride for treatment of gastroesophageal reflux disease along with the improvement of moisture stability to get better therapeutic efficacy. Materials and Methods: Pan coating technique was used for coating of the tablet. Film coating was done using Eudragit RLPO and Eugragit EPO as coating polymer. 32 full factorial design was applied for optimization purpose, and 9 runs were conducted. In that Eudragit RLPO and Eudragit EPO taken as an independent variables and moisture gain and Cummulative Drug Release (CDR) were taken as dependent variables. Drug and excipient compatibility was done using differential scanning calorimetry and Fourier transform infrared spectroscopy study. The tablet was evaluated for precompression parameter and all postcompression parameter. Stability study was carried out at room temperature (30°C ± 2°C/65% ± 5% relative humidity). Final formulation was compared with marketed formulation RANTEC 300. Result: Tablets were passing out all precompression parameter along with postcompression parameter. Stability study shows that the parameter such as hardness, friability, and dissolution are in the range. Hence, there is no significant change shown after stability study. Our final formulation was compared with marketed formulation RANTEC 300 and result demonstrates that our final formulation have less moisture gain and give release up to 12 h. Conclusion: The result of present study demonstrates that final formulation has less moisture gain and getting desired CDR for sustained release of drug. On the basis of all study, it was concluded that the tablet was coated by combination of Eudragit RLPO 10% and Eudragit EPO 10% give better result. This formation provided promising approach for the drug release up to 12 h for moisture sensitive drug like ranitidine hydrochloride. PMID:25838994

  5. Single and Dual Drug Release Patterns from Shellac Wax-Lutrol Matrix Tablets Fabricated with Fusion and Molding Techniques

    PubMed Central

    Phaechamud, T.; Choncheewa, C.

    2015-01-01

    The objective of this investigation was to prepare the shellac wax matrix tablets by fusion and molding technique incorporated with Lutrol in different ratios to modify the hydrophobicity of matrix tablet. The matrix tablets with single drug were loaded either with propranolol hydrochloride or hydrochlorothiazide as hydrophilic and hydrophobic model drugs, and a dual drug formula was also prepared. The single and dual drug release patterns were studied in a dissolution apparatus using distilled water as medium. Propranolol hydrochloride released from matrix was easier than hydrochlorothiazide. Drug release from shellac wax matrix could be enhanced by incorporation of Lutrol. However retardation of drug release from some matrix tablets was evident for the systems that could form dispersion in the dissolution medium. The gel network from high content of Lutrol was hexagonal which was a dense and more compact structure than the other structures found when low amounts of Lutrol were present in the formula. Therefore, the formulae with high content of Lutrol could prolong drug release more efficiently than those containing low content of Lutrol. Hence shellac wax matrix could modulate the drug release with the addition of Lutrol. Sustainable dual drug release was also obtained from these developed matrix tablets. Thus shellac wax-Lutrol component could be used as a potential matrix tablet prepared with fusion and molding technique with excellent controlled drug release. PMID:25767320

  6. Drug release characteristics from chitosan-alginate matrix tablets based on the theory of self-assembled film.

    PubMed

    Li, Liang; Wang, Linlin; Shao, Yang; Ni, Rui; Zhang, Tingting; Mao, Shirui

    2013-06-25

    The aim of this study was to better understand the underlying drug release characteristics from chitosan-alginate matrix tablets containing different types of drugs. Theophylline, paracetamol, metformin hydrochloride and trimetazidine hydrochloride were used as model drugs exhibiting significantly different solubilities (12, 16, 346 and >1000 mg/ml at 37 °C in water). A novel concept raised was that drugs were released from chitosan-alginate matrix tablets based on the theory of a self-assembled film-controlled release system. The film was only formed on the surface of tablets in gastrointestinal environment and originated from chitosan-alginate polyelectrolyte complex, confirmed by differential scanning calorimetry characterization. The formed film could decrease the rate of polymer swelling to a degree, also greatly limit the erosion of tablets. Drugs were all released through diffusion in the hydrated matrix and polymer relaxation, irrespective of the drug solubility. The effects of polymer level and initial drug loading on release depended on drug properties. Drug release was influenced by the change of pH. In contrast, the impact of ionic strength of the release medium within the physiological range was negligible. Importantly, hydrodynamic conditions showed a key factor determining the superiority of the self-assembled film in controlling drug release compared with conventional matrix tablets. The new insight into chitosan-alginate matrix tablets can help to broaden the application of this type of dosage forms.

  7. Behaviors of controlled drug release of magnetic-gelatin hydrogel coated stainless steel for drug-eluting-stents application

    NASA Astrophysics Data System (ADS)

    Huang, Li-Ying; Yang, Ming-Chien

    2007-03-01

    The behavior of drug release controlled by magnetic fields (MF) for stainless steel coated with magnetic-gelatin (MAG-GE) hydrogel was investigated in this paper. X-ray photoelectron spectroscope (XPS) and vibrating sample magnetometer were used to evaluate the characterizations of MAG-GE hydrogel and the interaction with the surface of SUS316L. A model drug (sirolimus) was loaded to the MAG-GE hydrogel. When applying MF to the MAG-GE hydrogel, the sirolimus release rate of the magnetic hydrogel decreased by {1}/{3}, comparing to that without the field. This suggests a "close" configuration of the MAG-GE hydrogel due to the aggregation of magnetic nanoparticles which reduced the pore size of MAG-GE hydrogel.

  8. Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers.

    PubMed

    Sun, Dajun D; Lee, Ping I

    2015-08-10

    The objective of the current study is to mechanistically differentiate the dissolution and supersaturation behaviors of amorphous drugs from amorphous solid dispersions (ASDs) based on medium-soluble versus medium-insoluble carriers under nonsink dissolution conditions through a direct head-to-head comparison. ASDs of indomethacin (IND) were prepared in several polymers which exhibit different solubility behaviors in acidic (pH1.2) and basic (pH7.4) dissolution media. The selected polymers range from water-soluble (e.g., PVP and Soluplus) and water-insoluble (e.g., ethylcellulose and Eudragit RL PO) to those only soluble in an acidic or basic dissolution medium (e.g., Eudragit E100, Eudragit L100, and HPMCAS). At 20wt.% drug loading, DSC and powder XRD analysis confirmed that the majority of incorporated IND was present in an amorphous state. Our nonsink dissolution results confirm that whether the carrier matrix is medium soluble determines the release mechanism of amorphous drugs from ASD systems which has a direct impact on the rate of supersaturation generation, thus in turn affecting the evolution of supersaturation in amorphous systems. For example, under nonsink dissolution conditions, the release of amorphous IND from medium-soluble carriers is governed by a dissolution-controlled mechanism leading to an initial surge of supersaturation followed by a sharp decline in drug concentration due to rapid nucleation and crystallization. In contrast, the dissolution of IND ASD from medium-insoluble carriers is more gradual as drug release is regulated by a diffusion-controlled mechanism by which drug supersaturation is built up gradually and sustained over an extended period of time without any apparent decline. Since several tested carrier polymers can be switched from soluble to insoluble by simply changing the pH of the dissolution medium, the results obtained here provide unequivocal evidence of the proposed transition of kinetic solubility profiles from the

  9. Oil-in-microgel strategy for enzymatic-triggered release of hydrophobic drugs.

    PubMed

    Busatto, C A; Labie, H; Lapeyre, V; Auzely-Velty, R; Perro, A; Casis, N; Luna, J; Estenoz, D A; Ravaine, V

    2017-05-01

    Polymer microgels have received considerable attention due to their great potential in the biomedical field as drug delivery systems. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan composed of N-acetyl-d-glucosamine and d-glucuronic acid. This polymer is biodegradable, nontoxic, and can be chemically modified. In this work, a co-flow microfluidic strategy for the preparation of biodegradable HA microgels encapsulating hydrophobic drugs is presented. The approach relies on: (i) generation of a primary oil-in-water (O/W) nanoemulsion by the ultrasonication method, (ii) formation of a double oil-in-water-in-oil emulsion (O/W/O) using microfluidics, and (iii) cross-linking of microgels by photopolymerization of HA precursors modified with methacrylate groups (HA-MA) present in the aqueous phase of the droplets. The procedure is used for the encapsulation and controlled release of progesterone. Degradability and encapsulation/release studies in PBS buffer at 37°C in presence of different concentrations of hyaluronidase are performed. It is demonstrated that enzymatic degradation can be used to trigger the release of progesterone from microgels. This method provides precise control of the release system and can be applied for the encapsulation and controlled release of different types of hydrophobic drugs.

  10. Effects of physicochemical properties of salting-out layer components on drug release.

    PubMed

    Tasaki, Hiroaki; Yoshida, Takayuki; Maeda, Atsushi; Katsuma, Masataka; Sako, Kazuhiro

    2009-07-06

    A "Salting-out Taste-masking System" generates a long lag time for numbness and bitterness masking, with subsequent immediate drug release to exert pharmacological effects. In this study, the effects of physicochemical properties of salting-out agents and water-soluble polymers in the salting-out layer on the dissolution behaviors of acetaminophen were investigated and predominant factors for lag time generation (Lag time index, hereafter LI) and subsequent drug release (Rapid release index, hereafter RI) were discussed. Each prepared formulation showed a different dissolution profile of acetaminophen with a lag time and subsequent immediate release. Significant correlations between both LI and RI and DeltaCST (the salting-out power of salting-out agents) (r(2)=0.90, 0.67, respectively) and between both LI and RI and CST(1) (the sensitivity of water-soluble polymers to a salting-out effect) (r(2)=0.98, 0.71, respectively) were shown. These results suggest that the components showing a strong salting-out effect inside the beads lead to extended lag times and slow drug releases after the lag times. Results further suggest the use of CST(1) to evaluate suitable combinations of salting-out agents and water-soluble polymers in this system.

  11. Effect of amine functionalization of spherical MCM-41 and SBA-15 on controlled drug release

    SciTech Connect

    Szegedi, A.; Popova, M.; Goshev, I.; Mihaly, J.

    2011-05-15

    MCM-41 and SBA-15 silica materials with spherical morphology and different particle sizes were synthesized and modified by post-synthesis method with 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, were carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N{sub 2} physisorption, thermal analysis, elemental analysis and FT-IR spectroscopy. Surface modification with amino groups resulted in high degree of ibuprofen loading and slow rate of release for MCM-41, whereas it was the opposite for SBA-15. The adsorbed drug content and the delivery rate can be predetermined by the choice of mesoporous material with the appropriate structural characteristics and surface functionality. -- Graphical Abstract: Ibuprofen delivery from the parent and amino-modified spherical MCM-41 materials with 100 nm (small) and 500 nm (large) particle sizes. Display Omitted Highlights: {yields} Spherical type MCM-41 and SBA-15 with different particle sizes were modified by APTES. {yields} Adsorption and release rate of ibuprofen were compared. {yields} High degree of ibuprofen loading, slow release rate for MCM-41, the opposite for SBA-15. {yields} MCM-41 with 100 nm particles was more stable and showed slower release rate

  12. Layered double hydroxides as supports for intercalation and sustained release of antihypertensive drugs

    NASA Astrophysics Data System (ADS)

    Xia, Sheng-Jie; Ni, Zhe-Ming; Xu, Qian; Hu, Bao-Xiang; Hu, Jun

    2008-10-01

    Zn/Al layered double hydroxides (LDHs) were intercalated with the anionic antihypertensive drugs Enalpril, Lisinopril, Captopril and Ramipril by using coprecipitation or ion-exchange technique. TG-MS analyses suggested that the thermal stability of Ena -, Lis - (arranged with monolayer, resulted from X-ray diffraction (XRD) and Fourier transform infrared spectra (FT-IR) analysis was enhanced much more than Cap - and Ram - (arranged with bilayer). The release studies show that the release rate of all samples markedly decreased in both pH 4.25 and 7.45. However, the release time of Ena -, Lis - were much longer compared with Cap -, Ram - in both pH 4.25 and 7.45, it is possible that the intercalated guests, arranged with monolayer in the interlayer, show lesser repulsive force and strong affinity with the LDH layers. And the release data followed both the Higuchi-square-root law and the first-order equation well. Based on the analysis of batch release, intercalated structural models as well as the TG-DTA results, we conclude that for drug-LDH, stronger the affinity between intercalated anions and the layers is, better the thermal property and the stability to the acid attack of drug-LDH, and the intercalated anions are easier apt to monolayer arrangement within the interlayer, were presented.

  13. Thermosensitive hydrogel for periodontal application: in vitro drug release, antibacterial activity and toxicity evaluation.

    PubMed

    Pakzad, Yousef; Ganji, Fariba

    2016-02-01

    Injectable thermosensitive chitosan hydrogel is an attractive temperature-induced sol-gel solution that is widely used in drug delivery and biomedical applications. In this study, an injectable antimicrobial delivery system for periodontal treatment based on chitosan/gelatin/β-glycerolphosphate solution has been developed. The result of thermal and mechanical evaluations of chitosan/gelatin/β-glycerolphosphate hydrogel showed that adding gelatin to chitosan/β-glycerolphosphate solution significantly decreased gelling time and increased gel strength at 37℃. The antimicrobial agents chosen for release studies were metronidazole with a low molecular weight and vancomycin hydrochloride with a high molecular weight. The initial burst and total in vitro drug release for metronidazole was 13% and 67%, respectively. The initial burst and total drug release for vancomycin hydrochloride was relatively low at 3% and 23%, respectively. The momentary and total percentage of metronidazole accumulated in the phosphate buffer revealed that chitosan/gelatin/β-glycerolphosphate can develop and maintain sustained release of metronidazole in concentrations that are effective for eliminating pathogenic bacteria over time. Cytotoxicity evaluations show that chitosan/gelatin/β-glycerolphosphate thermosensitive hydrogel is a drug carrier with no cytotoxic effects.

  14. Comparison of two hydrogel formulations for drug release in ophthalmic lenses.

    PubMed

    Paradiso, P; Galante, R; Santos, L; Alves de Matos, A P; Colaço, R; Serro, A P; Saramago, B

    2014-08-01

    In the present work two types of polymers were investigated as drug releasing contact lens materials: a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone hydrogel. The silicone hydrogel resulted from the addition of TRIS, a hydrophobic monomer containing silicon (3-tris(trimethylsilyloxy)silylpropyl 2-methylprop-2-enoate), to pHEMA. Both hydrogels were loaded with an antibiotic (levofloxacin) and an antiseptic (chlorhexidine) by soaking in the drug solutions. The hydrogel properties were determined to be within the range demanded for lens materials. The release profiles of both drugs from the hydrogels were obtained and eventual drug/polymer interactions were assessed with the help of Raman spectra. A mathematical model, developed to mimic the eye conditions, was applied to the experimental results in order to predict the in vivo efficacy of the studied systems. The release profiles were compared with those resulting from the application of commercial eyedrops. The pHEMA based hydrogel demonstrated to be the best material to achieve a controlled release of levofloxacin. In the case of chlorhexidine, the silicone hydrogel seems to lead to better results. In both cases, our results suggest that these materials are adequate for the preparation of daily disposable therapeutic contact lenses.

  15. Synthesis, characterization and drug release properties of 3D chitosan/clinoptilolite biocomposite cryogels.

    PubMed

    Dinu, Maria Valentina; Cocarta, Ana Irina; Dragan, Ecaterina Stela

    2016-11-20

    Three-dimensional (3D) biocomposites based on chitosan (CS) and clinoptilolite (CPL) were prepared by cryogelation and their potential application as drug carriers was investigated. Variation of CPL content from 0 to 33wt.% allowed the formation of biocomposites with heterogeneous morphologies consisting of randomly distributed pores. The further increase of CPL content led to ordered porous architectures where parallel pore channels were observed. The CPL content had a strong influence on water uptake, as well as on the cumulative release of diclofenac sodium (DS) and indomethacin (IDM). It was demonstrated that the drug delivery preferentially takes place in phosphate buffer saline (pH 7.4) in comparison to simulated gastric fluid (pH 1.2), where only a reduced drug release was observed. The drug release mechanism dominating these systems is described as a pseudo-Fickian diffusion, but it changes to non-Fickian release when 33wt.% of CPL was entrapped into the CS matrix or when IDM was loaded into biocomposites.

  16. Regulating the antibiotic drug release from β-tricalcium phosphate ceramics by atmospheric plasma surface engineering.

    PubMed

    Canal, C; Modic, M; Cvelbar, U; Ginebra, M-P

    2016-10-20

    Calcium phosphate (CaP) ceramics are of interest in bone substitution due to their good biocompatibility and bioresorbability. Currently certain CaPs in the market are loaded with antibiotics in order to prevent infections but further control is needed over antibiotic release patterns. Cold plasmas have emerged as a useful means of modifying the interactions with drugs through surface modification of polymer materials. In this work we explore the possibility of using atmospheric pressure plasmas as a tool for the surface modification of these CaP materials with newly populated bonds and charges, with views on enabling higher loading and controlled drug release. Herein the surface modification of β-tricalcium phosphate ceramics is investigated using an atmospheric pressure helium plasma jet as a tool for tuning the controlled release of the antibiotic doxycycline hyclate, employed as a drug model. The surface chemistry is tailored mainly by plasma jet surface interaction with an increasing O/C ratio without changes in the topography as well as by build-up of surface charges. With this surface tailoring it is demonstrated that the atmospheric plasma jet is a new promising tool that leads to the design of a control for drug release from bioceramic matrices.

  17. Magnetic field activated drug release system based on magnetic PLGA microspheres for chemo-thermal therapy.

    PubMed

    Fang, Kun; Song, Lina; Gu, Zhuxiao; Yang, Fang; Zhang, Yu; Gu, Ning

    2015-12-01

    Controlled drug delivery systems have been extensively investigated for cancer therapy in order to obtain better specific targeting and therapeutic efficiency. Herein, we developed doxorubicin-loaded magnetic PLGA microspheres (DOX-MMS), in which DOX was encapsulated in the core and high contents (28.3 wt%) of γ-Fe2O3 nanoparticles (IOs) were electrostatically assembled on the surface of microsphere to ensure the high sensitivity to response of an external alternating current magnetic field (ACMF). The IOs in PLGA shell can both induce the heat effect and trigger shell permeability enhancement to release drugs when DOX-MMs was activated by ACMF. Results show that the cumulative drug release from DOX-MMs exposed to ACMF for 30 min (21.6%) was significantly higher (approximately 7 times higher) than that not exposed to ACMF (2.8%). The combination of hyperthermia and enhanced DOX release from DOX-MMS is beneficial for in vitro 4T1 breast cancer cell apoptosis as well as effective inhibition of tumor growth in 4T1 tumor xenografts. Therefore, the DOX-MMS can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy.

  18. Modifying release characteristics from 3D printed drug-eluting products.

    PubMed

    Boetker, Johan; Water, Jorrit Jeroen; Aho, Johanna; Arnfast, Lærke; Bohr, Adam; Rantanen, Jukka

    2016-07-30

    This work describes an approach to modify the release of active compound from a 3D printed model drug product geometry intended for flexible dosing and precision medication. The production of novel polylactic acid and hydroxypropyl methylcellulose based feed materials containing nitrofurantoin for 3D printing purposes is demonstrated. Nitrofurantoin, Metolose® and polylactic acid were successfully co-extruded with up to 40% Metolose® content, and subsequently 3D printed into model disk geometries (ø10mm, h=2mm). Thermal analysis with differential scanning calorimetry and solid phase identification with Raman spectroscopy showed that nitrofurantoin remained in its original solid form during both hot-melt extrusion and subsequent 3D printing. Rheological measurements of the different compositions showed that the flow properties were sensitive to the amount of undissolved particles present in the formulation. Release of nitrofurantoin from the disks was dependent on Metolose® loading, with higher accumulated release observed for higher Metolose® loads. This work shows the potential of custom-made, drug loaded feed materials for 3D printing of precision drug products with tailored drug release characteristics.

  19. Drug release from extruded solid lipid matrices: theoretical predictions and independent experiments.

    PubMed

    Güres, Sinan; Siepmann, Florence; Siepmann, Juergen; Kleinebudde, Peter

    2012-01-01

    The aim of this study was to use a mechanistically realistic mathematical model based on Fick's second law to quantitatively predict the release profiles from solid lipid extrudates consisting of a ternary matrix. Diprophylline was studied as a freely water-soluble model drug, glycerol tristearate as a matrix former and polyethylene glycol or crospovidone as a pore former (blend ratio: 50:45:5%w/w/w). The choice of these ratios is based on former studies. Strains with a diameter of 0.6, 1, 1.5, 2.7 and 3.5mm were prepared using a twin-screw extruder at 65 °C and cut into cylinders of varying lengths. Drug release in demineralised water was measured using the USP 32 basket apparatus. Based on SEM pictures of extrudates before and after exposure to the release medium as well as on DSC measurements and visual observations, an analytical solution of Fick's second law of diffusion was identified in order to quantify the resulting diprophylline release kinetics from the systems. Fitting the model to one set of experimentally determined diprophylline release kinetics from PEG containing extrudates allowed determining the apparent diffusion coefficient of this drug (or water) in this lipid matrix. Knowing this value, the impact of the dimensions of the cylinders on drug release could be quantitatively predicted. Importantly, these theoretical predictions could be confirmed by independent experimental results. Thus, diffusion is the dominant mass transport mechanism controlling drug release in this type of advanced drug delivery systems. In contrast, theoretical predictions of the impact of the device dimensions in the case of crospovidone containing extrudates significantly underestimated the real diprophylline release rates. This could be attributed to the disintegration of this type of dosage forms when exceeding a specific minimal device diameter. Thus, mathematical modelling can potentially significantly speed up the development of solid lipid extrudates, but care has

  20. Synthesis of Depo-Medrol-chitosan hydrogel as new drug slow-release appliance and investigation of release kinetics by high-performance liquid chromatography.

    PubMed

    Alizadeh, Reza; Jabbari, Sara Majd; Zarnani, Amir H; Barghi, Hamidreza

    2016-09-01

    The present study deals with preparation and optimization of a novel chitosan hydrogel-based matrix by suspension cross-linking method for controlled release of Depo-Medrol. The controlled release of Depo-Medrol for effective Rheumatoid arthritis disease has become an imperative field in the drug delivery system. In this context, it was intended to optimize loading circumstances by experimental design and also study the release kinetics of Depo-Medrol entrapped in the chitosan matrix in order to obtain maximal efficiency for drug loading. The optimum concentrations of chitosan (2.5 g), glutaraldehyde (3.05 μL) and Depo-Medrol (0.1 mg) were set up to achieve the highest value of drug loaded and the most sustained release from the chitosan matrix. In vitro monitoring of drug release kinetic using high-performance liquid chromatography showed that 73% of the Depo-Medrol was released within 120 min, whereas remained drug was released during the next 67 h. High correlation between first-order and Higuchi's kinetic models indicates a controlled diffusion of Depo-Medrol through the surrounding media. Moreover, recovery capacity >82% and entrapment efficiency of 58-88% were achieved under optimal conditions. Therefore, the new synthesized Depo Medrol-chitosan is an applicable appliance for arthritis therapy by slow release mechanism. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Biodegradable gelatin-ciprofloxacin-montmorillonite composite hydrogels for controlled drug release and wound dressing application.

    PubMed

    Kevadiya, Bhavesh D; Rajkumar, Shalini; Bajaj, Hari C; Chettiar, Shiva Shankaran; Gosai, Kalpeshgiri; Brahmbhatt, Harshad; Bhatt, Adarsh S; Barvaliya, Yogesh K; Dave, Gaurav S; Kothari, Ramesh K

    2014-10-01

    This work reports intercalation of a sparingly soluble antibiotic (ciprofloxacin) into layered nanostructure silicate, montmorillonite (MMT) and its reaction with bone derived polypeptide, gelatin that yields three-dimensional composite hydrogel. Drug intercalation results in changes in MMT layered space and drug loaded MMT and gelatin creates 3D morphology with biodegradable composite hydrogels. These changes can be correlated with electrostatic interactions between the drug, MMT and the gelatin polypeptides as confirmed by X-ray diffraction patterns, thermal, spectroscopic analyses, computational modeling and 3D morphology revealed by SEM and TEM analysis. No significant changes in structural and functional properties of drug was found after intercalation in MMT layers and composite hydrogels. In vitro drug release profiles showed controlled release up to 150h. The drug loaded composite hydrogels were tested on lung cancer cells (A549) by MTT assay. The results of in vitro cell migration and proliferation assay were promising as composite hydrogels induced wound healing progression. In vitro biodegradation was studied using proteolytic enzymes (lysozyme and protease K) at physiological conditions. This new approach of drug intercalation into the layered nanostructure silicate by ion-exchange may have significant applications in cost-effective wound dressing biomaterial with antimicrobial property.

  2. Heat-Driven Release of a Drug Molecule From Carbon Nanotubes

    NASA Astrophysics Data System (ADS)

    Chaban, Vitaly; Prezhdo, Oleg

    2011-03-01

    Hydrophobicity and ability to absorb light that penetrates through living tissues make carbon nanotubes (CNTs) promising intracellular drug delivery agents. Following insertion of a drug molecule into a CNT, the latter is delivered into a tissue, is heated by near infrared radiation, and releases the drug. In order to assess the feasibility of this scheme, we investigate the rates of energy transfer between CNT, water and the drug molecule, and study the temperature and concentration dependence of the diffusion coefficient of the drug molecule inside CNTs. We use ciprofloxacin (CIP) as a sample drug: direct penetration of CIP through cell membranes is problematic due to its high polarity. The simulations show that a heated CNT rapidly deposits its energy to CIP and water. All estimated timescales for the vibrational energy exchange between CNT, CIP and water are less than 10 ps at 298 K. As the system temperature grows from 278 K to 363 K, the diffusion coefficient of the confined CIP increases 5-7 times, depending on CIP concentration. The diffusion coefficient slightly drops with increasing CIP concentration. This effect is more pronounced at higher temperatures. The simulations support the idea that optical heating of CNTs can assist in releasing encapsulated drugs.

  3. Drug release from E chemistry hypromellose tablets using the Bio-Dis USP type III apparatus: An evaluation of the effect of systematic agitation and ionic strength.

    PubMed

    Asare-Addo, Kofi; Supuk, Enes; Mahdi, Mohammed H; Adebisi, Adeola O; Nep, Elijah; Conway, Barbara R; Kaialy, Waseem; Al-Hamidi, Hiba; Nokhodchi, Ali

    2016-07-01

    The aim of the study was to evaluate the effect of systematic agitation, increasing ionic strength and gel strength on drug release from a gel-forming matrix (HPMC E10M, E4M and E50LV) using USP type III Bio-Dis apparatus with theophylline as a model drug. The triboelectric charging; particle sizing, water content, true density and SEM of all the hypromellose grades, theophylline and formulated blends were characterised. The results showed that balanced inter-particulate forces exist between drug particles and the excipient surface and this enabled optimum charge to mass ratio to be measured. Agitation and ionic strength affected drug release from E50LV and E4M tablet matrices in comparison to the E10M tablet matrices. Drug release increased substantially when water was used as the dissolution media relative to media at pH 1.2 (containing 0.4M NaCl). The results showed all f2 values for the E10M tablet matrices were above 50 suggesting the drug release from these tablet matrices to be similar. Rheological data also explained the different drug release behaviour with the stress required to yield/erode being 1Pa, 150Pa, and 320Pa, for the E50LV, E4M and E10M respectively. The stiffness of the gel was also found to be varied from 2.5Pa, 176.2Pa and 408.3Pa for the E50LV, E4M and E10M respectively. The lower G' value can be explained by a softer gel being formed after tablet introduction into the dissolution media thereby indicating faster drug release.

  4. Interpenetrating polymer network of locust bean gum-poly (vinyl alcohol) for controlled release drug delivery.

    PubMed

    Kaity, Santanu; Isaac, Jinu; Ghosh, Animesh

    2013-04-15

    A novel interpenetrating polymer network (IPN) microspheres of locust bean gum (LBG) and poly (vinyl alcohol) (PVA) was developed for oral controlled release of buflomedil hydrochloride (BH) by emulsion crosslinking method using glutaraldehyde as crosslinker. The effects of gum-polymer ratio, concentration of crosslinker and internal phase viscosity were evaluated thoroughly. Drug entrapment efficiency, particle size distribution, swelling property and in vitro release characteristics with kinetic modelling of microspheres were evaluated. The microspheres were characterised by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), solid state C(13) NMR, X-ray diffraction study (XRD) and differential scanning colorimetry (DSC). The microspheres showed control release property without showing any incompatibility in IPN device. Hence, IPN microspheres of LBG and PVA can be used as a potential carrier for controlled oral delivery of highly water soluble drugs like BH.

  5. Effect of methyl cellulose on gelation behavior and drug release from poloxamer based ophthalmic formulations.

    PubMed

    Dewan, Mitali; Bhowmick, Biplab; Sarkar, Gunjan; Rana, Dipak; Bain, Mrinal Kanti; Bhowmik, Manas; Chattopadhyay, Dipankar

    2015-01-01

    The effect of weight average molecular weight (Mw) of methyl cellulose (MC) on the gelation behavior of Poloxamer 407 (PM) and in vitro release of Ketorolac Tromethamine (KT) from different ophthalmic formulations based on PM is examined. A drop of gelation temperature of PM is observed using MC of various M(w) by test tube tilting method, UV-vis spectroscopy, viscometry and rheometry. It is also observed that the viscosity and gel strength of all the formulations are increased with the increase in Mw of MC. PM with highest Mw of MC provides best drug release property among all the formulations. It is evident from this investigation that there is a distinct effect of M(w) of MC on the gelation behavior of PM as well as on the drug release profile of KT from PM-MC based ophthalmic formulations.

  6. Basic butylated methacrylate copolymer/kappa-carrageenan interpolyelectrolyte complex: preparation, characterization and drug release behaviour.

    PubMed

    Prado, H J; Matulewicz, M C; Bonelli, P; Cukierman, A L

    2008-09-01

    The formation of a novel interpolyelectrolyte complex (IPEC) between basic butylated methacrylate copolymer and kappa-carrageenan was investigated and the product formed was characterized. Turbidity measurements and elemental analyses pointed to a 1:1 interaction of the repeating units. These results and FT-IR confirmed IPEC formation. Electronic microscopy images, particle size determination by image analysis and N(2) (77K) adsorption measurements were consistent with a porous material. This IPEC formed presented very good flowability and compactibility. Two maxima were observed in the swelling behaviour as a function of pH. The performance of the IPEC as a matrix for controlled release of drugs was evaluated, using ibuprofen as a model drug. Release profiles were properly represented by a mathematical model, which indicates that the system releases ibuprofen in a zero-order manner. These profiles could be controlled by conveniently modifying the proportion of the IPEC in the tablets.

  7. Tracking the intracellular drug release from graphene oxide using surface-enhanced Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Huang, Jie; Zong, Cheng; Shen, He; Cao, Yuhua; Ren, Bin; Zhang, Zhijun

    2013-10-01

    We have developed a graphene oxide (GO)-based nanoplatform simultaneously loaded with a chemical drug and Ag nanoparticles (NPs), and employed it to study the drug release from GO in living cells by surface-enhanced Raman spectroscopy (SERS). In our strategy, doxorubicin (DOX), a typical model anticancer drug, was loaded onto chemically prepared GO by means of π-π stacking, while the Ag NPs were covalently modified onto GO. After incubation of the DOX- and Ag NPs-loaded GO with Ca Ski cells for several hours, DOX will detach from the GO in an acidic environment due to the pH-dependent π-π interaction between DOX and GO. Real-time measurement of SERS signals of DOX using the GO loaded with Ag NPs as a SERS-active substrate allows us to monitor the process of the drug release inside the living cell. The SERS results reveal that DOX is initially released from the GO surface inside the lysosomes, then escapes into the cytoplasm, and finally enters the nucleus, while GO, the nanocarrier, remains within the cytoplasm, without entering the nucleus.We have developed a graphene oxide (GO)-based nanoplatform simultaneously loaded with a chemical drug and Ag nanoparticles (NPs), and employed it to study the drug release from GO in living cells by surface-enhanced Raman spectroscopy (SERS). In our strategy, doxorubicin (DOX), a typical model anticancer drug, was loaded onto chemically prepared GO by means of π-π stacking, while the Ag NPs were covalently modified onto GO. After incubation of the DOX- and Ag NPs-loaded GO with Ca Ski cells for several hours, DOX will detach from the GO in an acidic environment due to the pH-dependent π-π interaction between DOX and GO. Real-time measurement of SERS signals of DOX using the GO loaded with Ag NPs as a SERS-active substrate allows us to monitor the process of the drug release inside the living cell. The SERS results reveal that DOX is initially released from the GO surface inside the lysosomes, then escapes into the

  8. Effect of processing methods on drug release profiles of anti-restenotic self-assembled monolayers

    NASA Astrophysics Data System (ADS)

    Stoebner, Susan E.; Mani, Gopinath

    2012-04-01

    The use of anti-restenotic self-assembled monolayers (ARSAMs) has been previously demonstrated for delivering drugs from stents without polymeric carriers. ARSAMs have been prepared by coating an anti-restenotic drug (paclitaxel - PAT) on -COOH terminated phosphonic acid self-assembled monolayers (SAMs) coated Co-Cr alloy specimens. This study investigates the effect of different processing methods on the percentage of drug release from ARSAMs. The different methods that were used in this study to process ARSAMs include room temperature (RT) treatment, heat treatment (HT), cold treatment (CT) and quenching. The changes in polymorphism, chemical structure, morphology, and distribution of PAT on SAMs coated specimens were investigated using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and atomic force microscopy (AFM), respectively. DSC showed dihydrate, dehydrated dihydrate, semi-crystalline, and mixed (amorphous and dihydrate) forms of PAT for RT, HT, CT, and quenched specimens, respectively. FTIR showed that the chemical structure of PAT was unaltered in all the specimens processed by various methods employed in this study. SEM showed a mixture of spherical, ovoid, and bean-shaped morphologies of PAT on RT, HT, and CT while particle-like and needle-shaped morphologies of PAT were observed on quenched specimens. AFM showed PAT was uniformly distributed on RT, HT and CT specimens while particle-like PAT was well distributed and needle-shaped PAT was sparsely distributed on quenched specimens. CT specimens showed greater density of PAT crystals when compared to other methods. Thus, this study demonstrated that processing methods have significant influence on the polymorphism, morphology, and distribution of PAT on SAMs coated Co-Cr alloy specimens. The in vitro drug elution studies for up to 56 days showed sustained release for all the different groups of specimens. CT showed lesser

  9. Biointerfacing polymeric microcapsules for in vivo near-infrared light-triggered drug release.

    PubMed

    Shao, Jingxin; Xuan, Mingjun; Si, Tieyan; Dai, Luru; He, Qiang

    2015-12-07

    Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid release of encapsulated water-soluble drug. In vivo antitumor tests demonstrate that this microcapsule has the effective ability of inhibiting tumor growth and preventing metastases. Real time in vivo fluorescence imaging results confirm that capsules can be excreted gradually from the animal body which in turn demonstrates the biocompatibility and biodegradation of these biointerfacing GNR-microcapsules. This intelligent system provides a novel anticancer platform with the advantages of controlled release, biological friendliness and credible biosafety.

  10. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    NASA Astrophysics Data System (ADS)

    Andhariya, Nidhi; Upadhyay, Ramesh; Mehta, Rasbindu; Chudasama, Bhupendra

    2013-01-01

    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor—folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

  11. Polypyrrole Film as a Drug Delivery System for the Controlled Release of Risperidone

    NASA Astrophysics Data System (ADS)

    Svirskis, Darren; Travas-Sejdic, Jadranka; Rodgers, Anthony; Garg, Sanjay

    2009-07-01

    Conducting polymers are finding applications in medicine including drug delivery systems, biosensors and templates for the regeneration of nervous pathways. We aim to develop a novel system where the drug release rate can be controlled by electrical stimulation. Polypyrrole (PPY) is being used as a drug delivery system due to its inherent electrical conductivity, ease of preparation and apparent biocompatibility. Risperidone is an atypical antipsychotic drug used in the treatment of psychosis and related disorders, including schizophrenia. PPY was synthesised using p-toluene sulfonic acid as a primary dopant, in the presence of risperidone. A validated high performance liquid chromatography (HPLC) analytical method was used to quantify risperidone release. It has been demonstrated that the release rate of risperidone can be altered through the application, or absence, of electrical stimulation. Technology such as this would find use in drug-delivering implants where the dose could be adjusted through application of external stimulus, optimising benefit to side effect ratio, while simultaneously ensuring patient adherence (which is a particular challenge in mental health conditions).

  12. Hollow polycaprolactone composite fibers for controlled magnetic responsive antifungal drug release.

    PubMed

    Wang, Baolin; Zheng, Hongxia; Chang, Ming-Wei; Ahmad, Zeeshan; Li, Jing-Song

    2016-09-01

    Hollow magnetic fibers for trigger based drug release were synthesized using one-step co-axial electrospinning (COX-ES). This was achieved by encapsulating the antifungal active 'ketoconazole' (KCZ) and iron oxide (Fe3O4) nanoparticles (NPs) in composite form within the core shell polymeric matrix material (polycaprolactone, PCL) during the COX-ES process. Dimethyl silicone oil was used as the inner core (liquid) of co-flowing solutions, which subsequently perfused out of the two-phase electrospun microstructures to form hollow fibers. Resulting drug-loaded magnetic hollow fibers were characterized using optical microscopy, scanning electron microscopy and Fourier Transform Infra-Red. The tensile strength and magnetization properties of composite fibers were also assessed. KCZ drug concentration in electrospinning solutions strongly influenced resulting fiber morphology, drug loading efficiency and release. Expedited drug release during a slow-sustained phase was demonstrated through the application of an auxiliary magnetic field. Variations in tensile strength (∼1.3-6.3MPa) were due to composite fiber components compromising polymer chain integrity. In-vitro cell studies (using human cervical carcinoma cell lines) demonstrated fiber biocompatibility. The present study demonstrates the potential application of magnetic hollow fibers for controlled treatment of fungal infections and antimicrobial indications.

  13. Controlled release application of multilamellar vesicles: a novel drug delivery approach.

    PubMed

    Agnihotri, Sunil A; Soppimath, Kumaresh S; Betageri, Guru V

    2010-02-01

    A novel multilamellar vesicular delivery system was developed for the controlled release application. Multilamellar vesicles were prepared by thin film hydration and converted into proliposomes by freeze-drying. A model drug metoclopramide, a highly hydrophilic drug, was successfully encapsulated into proliposomes. The proliposomes produced were non-sticky, free-flowing powders. The proliposomes were formulated into a unit dosage form by combining with various excipients. The effect of different compositions such as type and concentration of phospholipid or hydrophilic polymer was investigared to optimize the formulation. The formation of multilamellar vesicles was confirmed by observing the process of hydration of proliposomes under an optical microscope. The spherical shape of vesicles was confirmed by transmission electron microscopy (TEM) and mean particle sizes were in the range of 1.3-2.5 microm, as measured by dynamic light scattering technique. Differential scanning calorimetry (DSC) study of formulations was conducted to understand the crystalline nature of drug in the vesicles. The results indicated a molecular level dispersion of drug into proliposomes with encapsulation efficiency up to 43%. Critical formulation parameters were identified to obtain a near zero order in vitro release pattern. Proliposomal formulations produced were suitable as multiparticulate drug delivery systems for the controlled release of a highly hydrophilic molecule.

  14. Preparation and drug release properties of norisoboldine-loaded chitosan microspheres.

    PubMed

    He, Miao; Wang, Haiyan; Dou, Wei; Chou, Guixin; Wei, Xiaohui; Wang, Zhengtao

    2016-10-01

    This study aimed to develop injectable norisoboldine (NOR) chitosan microspheres formulated through the emulsion cross-linking method. The formulation was optimized using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The morphology, size, physicochemical characterization and in vitro release behavior of the optimized formulation were evaluated. Scanning electron micrographs (SEM) indicated that the microspheres were spherical with a smooth surface. The encapsulation efficiency and drug loading content of the microspheres were 38.89%±1.72% and 4.25%±0.15%, respectively, with an average size of 105μm. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed the absence of a drug-polymer interaction and the amorphous nature of an entrapped drug. Analysis results of drug release in vitro show the burst release of the microsphere in 2h and a slow progression afterward. In vivo studies using Sprague-Dawley rats revealed that the NOR-loaded chitosan microspheres were biocompatible. This study suggests that the BBD with desired formulation could provide a suitable drug delivery system of chitosan microspheres.

  15. A multistep photothermic-driven drug release system using wire-framed Au nanobundles.

    PubMed

    Bang, Doyeon; Lee, Taeksu; Choi, Jihye; Park, Yeonji; Kim, Eunkyoung; Huh, Yong-Min; Haam, Seungjoo

    2015-01-28

    Here, wire-framed Au nanobundles (WNBs), which consist of randomly oriented and mutually connected Au wires to form a bundle shape, are synthesized. In contrast to conventional nanoparticles (spheres, rods, cubes, and stars), which exhibit nanostructure only on the surface, cross-sectional view image shows that WNBs have nanostructures in a whole volume. By using this specific property of WNBs, an externally controllable multistep photothermic-driven drug release (PDR) system is demonstrated for in vivo cancer treatment. In contrast to conventional nanoparticles that encapsulate a drug on their surface, WNBs preserve the drug payload in the overall inner volume, providing a drug loading capacity sufficient for cancer therapy. An improved in vivo therapeutic efficacy of PDR therapy is also demonstrated by delivering sufficient amount of drugs to the target tumor region.

  16. Electrospun water-stable zein/ethyl cellulose composite nanofiber and its drug release properties.

    PubMed

    Lu, Hangyi; Wang, Qingqing; Li, Guohui; Qiu, Yuyu; Wei, Qufu

    2017-05-01

    A simple and cost-effective way to prepare water-stable zein-based nanofibers for potential drug delivery was presented in this article. Corn protein zein was co-electrospun with hydrophobic ethyl cellulose. Indomethacin, as a model drug, was incorporated in situ into the composite nanofibers. Scanning electron microscopy and element mapping revealed the morphologies of drug-loaded nanofibers and drug distribution, respectively. Fourier transform infrared spectra confirmed the physical blending among the components. Differential scanning calorimetry and X-ray diffraction demonstrated the physical state of drug and polymers in the nanofiber matrix. The composite nanofibers showed a sustained diffusion-controlled release according to the results of in vitro dissolution tests.

  17. A general code to predict the drug release kinetics from different shaped matrices.

    PubMed

    Barba, Anna Angela; d'Amore, Matteo; Chirico, Serafina; Lamberti, Gaetano; Titomanlio, Giuseppe

    2009-02-15

    This work deals with the modeling of drug release from solid pharmaceutical systems (matrices) for oral delivery. The attention was paid to the behavior of matrices made of hydrogels and drug, and the modeling was devoted to reproduce all the relevant phenomena (water up-take, gel swelling, diffusivity increase, drug diffusion and polymer erosion). Thus, the transient mass balances (for both drug and water), with the proper initial and boundary conditions were written, and a generalized numerical code was formulated; it is able to describe several geometries (slab, sphere, infinite and finite cylinders; this latter was done by an approximation which reduces the 2D problem to an 1D scheme). The main phenomena observed in drug delivery from hydrogel-based matrix, i.e. polymer swelling and erosion, were taken into account. The code was validated by comparison with analytical solutions, available for some simplified situation, and then it was tested with some experimental data taken from literature.

  18. Community reentry challenges after release from prison among people who inject drugs in St. Petersburg, Russia

    PubMed Central

    Cepeda, Javier A.; Vetrova, Marina V.; Lyubimova, Alexandra I.; Levina, Olga S.; Heimer, Robert; Niccolai, Linda M.

    2016-01-01

    Purpose Little is known about the context of the post-release risk environment among formerly incarcerated people who inject drugs (PWID) in Russia. The purpose of this paper is to explore these challenges as they relate to reentry, relapse to injection opioid use, and overdose. Design/methodology/approach The authors conducted 25 in-depth semi-structured interviews among PWID living in St Petersburg, Russia who had been incarcerated within the past two years. Participants were recruited from street outreach (n = 20) and a drug treatment center (n = 5). Findings Emergent themes related to the post-release environment included financial instability, negative interactions with police, return to a drug using community, and reuniting with drug using peers. Many respondents relapsed to opioid use immediately after release. Those whose relapse occurred weeks or months after their release expressed more motivation to resist. Alcohol or stimulant use often preceded the opioid relapse episode. Among those who overdosed, alcohol use was often reported prior to overdosing on opioids. Practical implications Future post-release interventions in Russia should effectively link PWID to social, medical, and harm reduction services. Particular attention should be focussed on helping former inmates find employment and overdose prevention training prior to leaving prison that should also cover the heightened risk of concomitant alcohol use. Originality/value In addition to describing a syndemic involving the intersection of incarceration, injection drug use, poverty, and alcohol abuse, the findings can inform future interventions to address these interrelated public health challenges within the Russian setting. PMID:26277925

  19. Factors Affecting Release of Heat-Labile Enterotoxin by Enterotoxigenic Escherichia coli

    PubMed Central

    Kunkel, Steven L.; Robertson, Donald C.

    1979-01-01

    Various conditions affecting the release of heat-labile enterotoxin (LT) by enterotoxigenic Escherichia coli have been examined. The pH of a defined medium containing three amino acids, M-9 salts, and 0.5% glucose decreased to less than 7.0 in early log phase of growth, and no extracellular LT was detected. Adjustment of the pH at 8 h from 6.0 to 8.0 resulted in a concomitant increase in LT activity in culture supernatants. The release of cell-associated LT was significantly reduced by preincubation with protease inhibitors and increased by preincubation with trypsin. Cell-associated LT was not released by pH adjustment of cells grown at 21°C; however, polymyxin B treatment released a toxin species active in only the pigeon erythrocyte lysate (PEL) assay system. As the growth temperature was increased, polymyxin B released toxin species which exhibited both PEL and Y-1 adrenal tumor cell activity. Polymyxin B extracts of enterotoxigenic E. coli in early log phase grown at 37°C possessed only PEL activity, whereas extracts from cells in late-log and stationary phases had biological activity in both assay systems. Also, LT released by pH adjustment from mid-log to stationary phase was active in both PEL and Y-1 adrenal tumor cell assays. Gel electrophoresis of polymyxin B extracts revealed at least three molecular weight species active in either the PEL (22,000 daltons and 30,000 daltons) or both the PEL and the Y-1 adrenal tumor cell assay (72,000 daltons), depending on the growth temperature. These observations may help to explain the chemical and biological heterogeneity of most LT preparations and facilitate purification of LT by increasing the yield of enterotoxin. PMID:37162

  20. The systems containing clays and clay minerals from modified drug release: a review.

    PubMed

    Rodrigues, Luís Alberto de Sousa; Figueiras, Ana; Veiga, Francisco; de Freitas, Rivelilson Mendes; Nunes, Lívio César Cunha; da Silva Filho, Edson Cavalcanti; da Silva Leite, Cleide Maria

    2013-03-01

    Clays are materials commonly used in the pharmaceutical industry, either as ingredients or as active ingredients. It was observed that when they are administered concurrently, they may interact with drugs reducing their absorption. Therefore, such interactions can be used to achieve technological and biopharmaceutical advantages, regarding the control of release. This review summarizes bibliographic (articles) and technological (patents) information on the use of systems containing clays and clay minerals in modified drug delivery. In this area, formulations such natural clay, commercial clay, synthetic clay, composites clay-polymers, nanocomposites clay-polymers, films and hidrogels composites clay-polymers are used to slow/extend or vectorize the release of drugs and consequently they increase their bioavailability. Finally, this review summarizes the fields of technology and biopharmaceutical applications, where clays are applied.

  1. Vasorelaxant effect of nitric oxide releasing steroidal and nonsteroidal anti-inflammatory drugs

    PubMed Central

    Keeble, J; Al-Swayeh, O A; Moore, P K

    2001-01-01

    The effect of several nitric oxide releasing-non-steroidal anti-inflammatory drugs (NO-NSAID) and nitroprednisolone on blood vessel relaxation in vitro and in vivo was studied. Nitroflurbiprofen (NOF; EC50, 688.8±93.8 μM), nitroaspirin (NOA; EC50, 57.9±6.5 μM), nitroparacetamol (NOPARA; EC50, 71.5±14.6 μM) and nitroprednisolone (EC50, 15.1±1.4 μM) caused concentration-related relaxation of noradrenaline (NA)-contracted rat aortic rings. All NO releasing compounds tested were approximately three orders of magnitude less potent than sodium nitroprusside (SNP, EC50, 35.7±3.5 nM).The vasorelaxant effect of NOF and NOPARA in the rat aorta was potentiated by zaprinast (5 μM) and reduced by ODQ (5 μM). Flurbiprofen and paracetamol (100 μM) caused minimal (<10%) relaxation of the rat aorta and did not affect the response to SNP. The effect of NOF was unchanged in the presence of L-NAME (100 μM; EC30, 181.8±35.1 μM cf. EC30, 125.1±17.0 μM, P>0.05) but increased by removal of the endothelium (EC30, 164.3±26.3 μM cf. EC50, 688.8±93.8 μM, P<0.05).NOF (0.1–50 μM) produced a small but not concentration-related vasodilation of the NA-preconstricted (i.e. ‘high tone') perfused rat mesentery preparation (cf. SNP, EC30, 4.4±0.7 μM). In contrast, NOF (1–100 μM) produced concentration-related vasodilation of the ‘high tone' perfused rat kidney with an EC50 of 33.1±4.4 μM.Neither NOF (74 mg kg−1, i.p.) nor NOA (91.9 mg kg−1, i.p.) nor equimolar doses of flurbiprofen (50 mg kg−1, i.p.) or aspirin (50 mg kg−1, i.p.) affected mean arterial blood pressure (MAP) or heart rate (HR) of pentobarbitone-anaesthetized rats over a 1 h period.NO-NSAID relax blood vessels in vitro by an NO-dependent mechanism. The absolute vasorelaxant effect of NO releasing drug varies greatly with the choice of compound and between blood vessel preparations. PMID:11487511

  2. Water soluble drug releasing soft contact lens in response to pH of tears

    NASA Astrophysics Data System (ADS)

    Kim, G.; Noh, H.

    2016-06-01

    Human tear characteristics including pH and compositions can vary significantly depending on physical and environmental factors. Contact lenses directly contact with human tears can be swelled or de-swelled depending on the pH of the solution due to the nature of the hydrogel. For examples, anionic hydrogels, when the solution's pH is low, is shrunken due to the electric attraction force within the hydrogel network; the opposite phenomenon appears when the solution is basic. The purpose of this study was to evaluate the extent of water soluble drug, hydroxyl propyl methyl cellulose, released from contact lens according to the pH of the artificial tears. Artificial tears are prepared by mixing lysozyme, albumin, sodium chloride, potassium chloride, and calcium chloride following physiological concentrations. Hydrogel contact lens was thermally polymerized using HEMA, EGDMA, and AIBN. The prepared hydrogel lens was immersed in drug for 3 hours and the eluted drug mass was measured as a function of the time. As a result, the drug was released from the lens for 12 hours in all the pH of artificial tears. At the lower pH of artificial tears (pH 5.8), the total amount of dye emitted from the lens was increased than the total amount of dye emitted at the basic tear (pH 8.4). Also, initial burst at acidic tears was increased within 1 hour. Release pattern of water-soluble drug from hydrogel lens turned out to be different depending on the pH of the artificial tears. When designing drug releasing contact lens, physiological pH of tears should be considered.

  3. Impact of physicochemical properties of porous silica materials conjugated with dexamethasone via pH-responsive hydrazone bond on drug loading and release behavior

    NASA Astrophysics Data System (ADS)

    Numpilai, Thanapha; Witoon, Thongthai; Chareonpanich, Metta; Limtrakul, Jumras

    2017-02-01

    The conjugation of dexamethasone (DEX) onto modified-porous silica materials via a pH-responsive hydrazone bond has been reported to be highly efficient method to specifically deliver the DEX to diseased sites. However, the influence of physicochemical properties of porous silica materials has not yet been fully understood. In this paper, the impact of pore sizes, particle sizes and silanol contents on surface functionalization, drug loading and release behavior of porous silica materials conjugated with dexamethasone via pH-responsive hydrazone bond was investigated. The grafting density was found to relate to the number of silanol groups on the surface of porous silica materials. The particle size and macropores of the porous silica materials played an vital role on the drug loading and release behavior. Although the porous silica materials with larger particle sizes possessed a lower grafting density, a larger amount of drug loading could be achieved. Moreover, the porous silica materials with larger particle sizes showed a slower release rate of DEX due to a longer distance for cleaved DEX diffusion out of pores. DEX release rate exhibited pH-dependent, sustained release. At pH 4.5, the amount of DEX release within 10 days could be controlled in the range of 12.74-36.41%, depending on the host material. Meanwhile, less than 1.5% of DEX was released from each of type of the porous silica materials at pH 7.4. The results of silica dissolution suggested that the degradation of silica matrix did not significantly affect the release rate of DEX. In addition, the kinetic modeling studies revealed that the DEX releases followed Korsmeyer-Peppas model with a release exponent (n) ranged from 0.3 to 0.47, indicating a diffusion-controlled release mechanism.

  4. Tunable release of multiclass anti-HIV drugs that are water-soluble and loaded at high drug content in polyester blended electrospun fibers

    PubMed Central

    Carson, Daniel; Jiang, Yonghou; Woodrow, Kim

    2015-01-01

    Objectives Sustained release of small molecule hydrophilic drugs at high doses remains difficult to achieve from electrospun fibers and limits their use in clinical applications. Here we investigate tunable release of several water-soluble anti-HIV drugs from electrospun fibers fabricated with blends of two biodegradable polyesters. Methods Drug-loaded fibers were fabricated by electrospinning using ratios of PCL and PLGA. Fiber morphology was imaged using SEM, and DSC was used to measure thermal properties. HPLC was used to measure drug loading and release from fibers. Cytotoxicity and antiviral activity of drug-loaded fibers were measured in an in vitro cell culture assay. Results We show programmable release of hydrophilic antiretroviral drugs loaded up to 40 wt%. Incremental tuning of highly-loaded drug fibers within 24 hours or >30 days was achieved by controlling the ratio of PCL and PLGA. Fiber compositions containing higher PCL content yielded greater burst release whereas fibers with higher PLGA content resulted in greater sustained release kinetics. We also demonstrated that our drug-loaded fibers are safe and can sustain inhibition of HIV in vitro. Conclusions These data suggest that we were able to overcome current limitations associated with sustained release of small hydrophilic drugs at clinically relevant doses. We expect that our system represents an effective strategy to sustain delivery of water-soluble molecules that will benefit a variety of biomedical applications. PMID:26286184

  5. Against Their Wills: Children Born Affected by Drugs.

    ERIC Educational Resources Information Center

    Hodgkinson, Harold L.; Outtz, Janice Hamilton

    There is no national policy on assisting drug-using pregnant mothers nor on the children they produce. This paper looks at the issue of "crack-cocaine" and mothers who give birth to children after using drugs during pregnancy. It attempts to lay out what is known, and it puts forth "best guesses" regarding helping children born…

  6. Guide to Children Affected by Parental Drug Abuse

    ERIC Educational Resources Information Center

    Davies, Leah

    2010-01-01

    A conservative estimate is that one in six children in school today has a parent dependent on or addicted to alcohol or other drugs. This places these students at high risk for social and emotional problems, as well as for school failure, drug use, and delinquency. Schools, however, are a logical place to reach them. Identifying children of those…

  7. Drug reactions affecting the nail unit: diagnosis and management.

    PubMed

    Piraccini, Bianca Maria; Iorizzo, Matilde

    2007-04-01

    Several drugs may be responsible for the development of nail abnormalities, but only a few classes are consistently associated with nail symptoms. Drug-induced nail abnormalities result from toxicity to the matrix, the nail bed, the periungual tissues, or the digit blood vessels. Pharmacologic agents that most frequently produce nail abnormalities include retinoids, indinavir, and cancer chemotherapeutic agents.

  8. Diffusion-Based Design of Multi-Layered Ophthalmic Lenses for Controlled Drug Release.

    PubMed

    Pimenta, Andreia F R; Serro, Ana Paula; Paradiso, Patrizia; Saramago, Benilde; Colaço, Rogério

    2016-01-01

    The study of ocular drug delivery systems has been one of the most covered topics in drug delivery research. One potential drug carrier solution is the use of materials that are already commercially available in ophthalmic lenses for the correction of refractive errors. In this study, we present a diffusion-based mathematical model in which the parameters can be adjusted based on experimental results obtained under controlled conditions. The model allows for the design of multi-layered therapeutic ophthalmic lenses for controlled drug delivery. We show that the proper combination of materials with adequate drug diffusion coefficients, thicknesses and interfacial transport characteristics allows for the control of the delivery of drugs from multi-layered ophthalmic lenses, such that drug bursts can be minimized, and the release time can be maximized. As far as we know, this combination of a mathematical modelling approach with experimental validation of non-constant activity source lamellar structures, made of layers of different materials, accounting for the interface resistance to the drug diffusion, is a novel approach to the design of drug loaded multi-layered contact lenses.

  9. Diffusion-Based Design of Multi-Layered Ophthalmic Lenses for Controlled Drug Release

    PubMed Central

    Pimenta, Andreia F. R.; Serro, Ana Paula; Paradiso, Patrizia; Saramago, Benilde

    2016-01-01

    The study of ocular drug delivery systems has been one of the most covered topics in drug delivery research. One potential drug carrier solution is the use of materials that are already commercially available in ophthalmic lenses for the correction of refractive errors. In this study, we present a diffusion-based mathematical model in which the parameters can be adjusted based on experimental results obtained under controlled conditions. The model allows for the design of multi-layered therapeutic ophthalmic lenses for controlled drug delivery. We show that the proper combination of materials with adequate drug diffusion coefficients, thicknesses and interfacial transport characteristics allows for the control of the delivery of drugs from multi-layered ophthalmic lenses, such that drug bursts can be minimized, and the release time can be maximized. As far as we know, this combination of a mathematical modelling approach with experimental validation of non-constant activity source lamellar structures, made of layers of different materials, accounting for the interface resistance to the drug diffusion, is a novel approach to the design of drug loaded multi-layered contact lenses. PMID:27936138

  10. Chemosterilization of male sea lampreys (Petromyzon marinus) does not affect sex pheromone release

    USGS Publications Warehouse

    Siefkes, Michael J.; Bergstedt, Roger A.; Twohey, Michael B.; Li, Weiming

    2003-01-01

    Release of males sterilized by injection with bisazir is an important experimental technique in management of sea lamprey (Petromyzon marinus), an invasive, nuisance species in the Laurentian Great Lakes. Sea lampreys are semelparous and sterilization can theoretically eliminate a male's reproductive capacity and, if the ability to obtain mates is not affected, waste the sex products of females spawning with him. It has been demonstrated that spermiating males release a sex pheromone that attracts ovulating females. We demonstrated that sterilized, spermiating males also released the pheromone and attracted ovulating females. In a two-choice maze, ovulating females increased searching behavior and spent more time in the side of the maze containing chemical stimuli from sterilized, spermiating males. This attraction response was also observed in spawning stream experiments. Also, electro-olfactograms showed that female olfactory organs were equally sensitive to chemical stimuli from sterilized and nonsterilized, spermiating males. Finally, fast atom bombardment mass spectrometry showed that extracts from water conditioned with sterilized and nonsterilized, spermiating males contained the same pheromonal molecule at similar levels. We concluded that injection of bisazir did not affect the efficacy of sex pheromone in sterilized males.

  11. Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood

    PubMed Central

    Krstew, Elena V.; Tait, Robert J.; Hulse, Gary K.

    2012-01-01

    Naltrexone is not recommended during pregnancy. However, sustained-release naltrexone implant use in humans has resulted in cases of inadvertent foetal exposure. Here, we used clinically relevant dosing to examine the effects of maternally administered sustained-release naltrexone on the rat brain by examining offspring at birth and in adulthood. Maternal treatment (naltrexone or placebo implant) started before conception and ceased during gestation, birth or weaning. Morphometry was assessed in offspring at birth and adulthood. Adult offspring were evaluated for differences in locomotor behaviour (basal and morphine-induced, 10 mg/kg, s.c.) and opioid neurochemistry, propensity to self-administer morphine and cue-induced drug-seeking after abstinence. Blood analysis confirmed offspring exposure to naltrexone during gestation, birth and weaning. Naltrexone exposure increased litter size and reduced offspring birth-weight but did not alter brain morphometry. Compared to placebo, basal motor activity of naltrexone-exposed adult offspring was lower, yet they showed enhanced development of psychomotor sensitization to morphine. Developmental naltrexone exposure was associated with resistance to morphine-induced down-regulation of striatal preproenkephalin mRNA expression in adulthood. Adult offspring also exhibited greater operant responding for morphine and, in addition, cue-induced drug-seeking was enhanced. Collectively, these data show pronounced effects of developmental naltrexone exposure, some of which persist into adulthood, highlighting the need for follow up of humans that were exposed to naltrexone in utero. PMID:23300784

  12. Drug release from interpenetrating polymer networks based on poly(ethylene glycol) methyl ether acrylate and gelatin.

    PubMed

    Ding, Frank; Hsu, S-H; Wu, D-H; Chiang, W-Y

    2009-01-01

    In order to develop new materials for biomedical and pharmaceutical applications, interpenetrating polymer networks (IPNs) based on poly(ethylene glycol) methyl ether acrylate (PEGMEA) and gelatin were synthesized. These two materials were cross-linked sequentially using N,N'-methylene bisacrylamide (NMBA) and glutaraldehyde (Glu). Two series of IPNs gels were synthesized by applying different amounts of PEGMEA and gelatin in the initial feed. Sequential IPNs were prepared by polymerizing and cross-linking PEGMEA in the presence of gelatin using redox initiators (e.g., ammonium peroxydisulfate (APS) and N,N,N',N'-tetramethyl ethylenediamine (TEMED)), as well as NMBA as the cross-linking agent. Gelatin in firm gel was then cross-linked with 1% glutaraldehyde. The swelling kinetics, mechanical properties and drug-release behavior of these IPNs were analyzed. The surface properties were examined by scanning electron microscopy. The results indicated that the swelling ratio decreased with an increase in the content of both PEGMEA and gelatin in the IPNs. PEGMEA/gelatin-based full-IPNs had a significantly higher shear modulus (G) and cross-linking density (rho) when the content of PEGMEA was increased. The drug loading was very high due to the full-IPN structure. The drug-release velocity was mainly affected by the content of PEGMEA.

  13. Loading and release of amine drugs by ion-exchange fibers: role of amine type.

    PubMed

    Gao, Yanan; Liu, Hongzhuo; Yuan, Jing; Yang, Yang; Che, Xin; Hou, Yanlong; Li, Sanming

    2014-04-01

    With more production and application of ion-exchange fibers (IEFs), it becomes necessary to understand the interaction between IEFs and amine compounds, an important group of organic drugs and structural components of large organic molecules in biological systems. However, so far few experimental studies have been conducted to systematically investigate the exchanging mechanism of amine compounds to IEFs. Therefore, 15 amine drugs were selected to investigate the effect of amine type on the loading and release of them from the related IEFs. Loading affinity of these drugs by IEFs decreased in the order of secondary, tertiary, and primary. The following items: basicity, aromaticity, molar volume, rotatability, and so on, were emphatically discussed to address the underlying mechanism of drug loading and releasing extent and rate of IEFs. It was evident that strong alkaline drugs strengthened the ionic bond between the amine groups and IEFs, and thus the loading affinity. These results will advance the understanding of the exchanging behavior of IEFs in the drug delivery system.

  14. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies

    PubMed Central

    Gaur, Praveen Kumar; Mishra, Shikha; Bajpai, Meenakshi; Mishra, Anushika

    2014-01-01

    Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5 ± 3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75 ± 5% relative humidity (RH) for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (Cmax⁡) and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES). PMID:24967360

  15. Release mechanisms of a sparingly water-soluble drug from controlled porosity-osmotic pump pellets using sulfobutylether-beta-cyclodextrin as both a solubilizing and osmotic agent.

    PubMed

    Sotthivirat, Sutthilug; Haslam, John L; Lee, Ping I; Rao, Venkatramana M; Stella, Valentino J

    2009-06-01

    The purpose of this work is to delineate the release mechanisms of a sparingly water-soluble drug, prednisolone (PDL), from a microporous or controlled porosity-osmotic pump pellet (CP-OPP) using sulfobutylether-beta-cyclodextrin (CD) as both a solubilizing and osmotic agent. All factors, osmotic and diffusional, influencing drug release as described by the Theeuwes and Zentner equation were partially demonstrated in an earlier paper1 and are further quantitatively evaluated here to determine whether the equation may be applied to CP-OPPs. The PDL release rate from the CP-OPPs containing precomplexed PDL follows the zero-order kinetics for up to 30-40% of drug release during the first 1-2 h and subsequently nonzero order kinetics. The zero-order drug release phase reveals the main contribution is from osmotic pumping with a negligible diffusion component, resulting from the nearly constant driving forces in the system. The nonzero order drug release phase is associated with the dynamic changes in the system (e.g., declining osmotic driving force and greater diffusion component with time). In addition, the parameters related to membrane characteristics were determined, and the effect of viscosity was evaluated for the pellet system. The membranes coated on the CP-OPPs are less permeable to water or solutes than the membranes coated on the previously reported tablets. The viscosity due to the CD decreases as a function of CD concentration, which partly affects the observed drug release profiles. The viscosity effect of CD is significant and captured in a hydraulic permeability term.

  16. Preparation, Drug Releasing Property and Pharmacodynamics of Soy Isoflavone-Loaded Chitosan Microspheres

    PubMed Central

    Du, Zhongyan; Dou, Xiaobing; Huang, Chenyun; Gao, Jia; Hu, Linfeng; Zhu, Jiazhen; Qian, Ying; Dou, Minhua; Fan, Chunlei

    2013-01-01

    Soybean isoflavone (SIF) has anti-aging properties and many other biological functions; however, SIF is difficult to reach higher blood concentration due to its rapid metabolism. Therefore, it is of great value to design and produce a sustained-release formulation that is able to maintain a stable level of plasma concentrations. In this paper, soybean isoflavone sustained-release microsphere from chitosan and sodium alginate was prepared successfully. The important factors that determined the quality of the microspheres were the sodium alginate concentration in solution B, the ratio of soybean isoflavone to chitosan and the mixing speed. The relative yield, encapsulation efficiency and drug loading capability of SIF were much higher than the existing commercial formulations. In real gastrointestinal conditions, compared with the non-sustained release group, the release rate of SIF slowed down and the reaction time was prolonged. Animal experiments showed that sustained-release microspheres intensified the anti-aging potentials of SIF. Compared with the Non-sustained release (NSR) group mice, oral SIF/CHI microsphere treated mice were better in the Morris Water Maze Test (MWMT), the MDA level in the both plasma and brain of the sustained release(SR) group mice decreased, and SOD content was remarkably improved. PMID:24244544

  17. Influence of cholesterol on liposome stability and on in vitro drug release.

    PubMed

    Briuglia, Maria-Lucia; Rotella, Chiara; McFarlane, Amber; Lamprou, Dimitrios A

    2015-06-01

    Cholesterol plays a strategic role in liposome composition; however, the quantity used to achieve an appropriate formulation has not been yet clarified. Therefore, by screening arrangement of lipids and cholesterol ratio, the main aim of this study is to investigate the most suitable amount of cholesterol in lipids in order to prepare stable and controlled drug release vehicles. For the preparation of liposomes, DMPC, DPPC and DSPC phospholipids were used and combined with different molar ratios of cholesterol (e.g. 100, 80-20, 70-30, 60-40 and 50-50%). Stability studies were conducted by storing the formulations at 37 and 50 °C for 30 days and by analysing them by AFM, DLS and FT-IR. By detecting the two most stable formulations from the stability results, drug encapsulation and in vitro release studies in PBS were performed by encapsulating atenolol and quinine. The release results were validated using a simulation model to ensure the reliability and suitable interpretation of the data. The generated model showed a good correlation between the prediction and the in vitro obtained results. By using 70:30% ratio (known in literature as 2:1), it is possible to reach the most stable formulation to guarantee a controlled and reproducible release for drugs with different physicochemical characteristics and pharmaceutical applications.

  18. Statistical assessment of dissolution and drug release profile similarity using a model-dependent approach.

    PubMed

    Berry, Mark R; Likar, Michael D

    2007-10-18

    A general multivariate procedure for assessing the similarity of dissolution and drug release profiles was developed. A mathematical model is fit to the data, and Hotelling's T(2) test is used to calculate the joint confidence region around the vector of differences between least-squares estimates of the parameters in the model. The method of Lagrange multipliers is used to determine if this confidence region is enclosed within a predetermined similarity region, and profile similarity is claimed if this is the case. The first-order, Gompertz, logistic, second-order, and Weibull models were fit to the in vitro extended-release profile of pseudoephedrine HCl from an asymmetric membrane (AM) film-coated osmotic tablet. The first-order model was selected because of its simplicity and because it was the best-fitting model according to a modified form of Akaike's Information Criterion. A nonlinear response surface model was also developed so that the formulator could calculate how much of the AM film coat should be applied in order to obtain the desired drug release profile. The usefulness of this model-dependent procedure was further demonstrated during an analytical method transfer exercise, where it was used to compare the drug release profiles obtained by two independent laboratories; additional research is required, however, before the appropriate acceptance criteria for demonstrating profile similarity can be recommended.

  19. Chitosan/alginate based multilayers to control drug release from ophthalmic lens.

    PubMed

    Silva, Diana; Pinto, Luís F V; Bozukova, Dimitriya; Santos, Luís F; Serro, Ana Paula; Saramago, Benilde

    2016-11-01

    In this study we investigated the possibility of using layer-by-layer deposition, based in natural polymers (chitosan and alginate), to control the release of different ophthalmic drugs from three types of lens materials: a silicone-based hydrogel recently proposed by our group as drug releasing soft contact lens (SCL) material and two commercially available materials: CI26Y for intraocular lens (IOLs) and Definitive 50 for SCLs. The optimised coating, consisting in one double layer of (alginate - CaCl2)/(chitosan+glyoxal) topped with a final alginate-CaCl2 layer to avoid chitosan degradation by tear fluid proteins, proved to have excellent features to control the release of the anti-inflammatory, diclofenac, while keeping or improving the physical properties of the lenses. The coating leads to a controlled release of diclofenac from SCL and IOL materials for, at least, one week. Due to its high hydrophilicity (water contact angle≈0) and biocompatibility, it should avoid the use of further surface treatments to enhance the useŕs comfort. However, the barrier effect of this coating is specific for diclofenac, giving evidence to the need of optimizing the chemical composition of the layers in view of the desired drug.

  20. Development of an Inhaled Sustained Release Dry Powder Formulation of Salbutamol Sulphate, an Antiasthmatic Drug.

    PubMed

    Kumaresan, C; Sathishkumar, K

    2016-01-01

    The present research was aimed to develop and characterize a sustained release dry powder inhalable formulation of salbutamol sulphate. The salbutamol sulphate microparticles were prepared by solvent evaporation method using biodegradable polymer poly (D,L-lactic-co-glycolic acid) to produce salbutamol sulphate microparticle mixed with carrier respirable grade lactose for oral inhalation of dry powder. The drug content were estimated to produce 1 mg sustained release salbutamol sulphate per dose. Total four formulations K1, K2, K3 and K4 were prepared with 1:1, 1:2, 1:3, 1:4 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid). The developed formulations were studied for physicochemical properties, in vitro drug relase and Anderson cascade impaction studies. The prepared formulations effectively releases drug for 12 h in diffusion bag studies. Based on dissolution performance the 1:1 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid) produces in vitro release 92.57% at 12 h and having particle size of microparticles (D0.5μm) 5.02±0.6 and the pulmonary deposition of dry powder 34.5±3.21 (respiratory fraction in percentage).

  1. Evaluation of photodynamic activity, photostability and in vitro drug release of zinc phthalocyanine-loaded nanocapsules.

    PubMed

    de Souza, Thiane Deprá; Ziembowicz, Francieli Isa; Müller, Debora Friedrich; Lauermann, Sâmera Cristina; Kloster, Carmen Luisa; Santos, Roberto Christ Vianna; Lopes, Leonardo Quintana Soares; Ourique, Aline Ferreira; Machado, Giovanna; Villetti, Marcos Antonio

    2016-02-15

    Nanocapsule formulations containing zinc phthalocyanine (ZnPc) were investigated as drug delivery systems for use in photodynamic therapy (PDT). ZnPc loaded chitosan, PCL, and PCL coated with chitosan nanocapsules were prepared and characterized by means of their physicochemical properties, photodynamic activity, photostability and drug release profile. All formulations presented nanometric hydrodynamic radius, around 100 nm, low polydispersity index (0.08-0.24), slightly negative zeta potential for PCL nanoparticles and positive zeta potential for suspension containing chitosan. Encapsulation efficiencies were higher than 99%. The capacity of ZnPc loaded nanocapsules to produce cytotoxic singlet oxygen ((1)O2) by irradiation with red laser was monitored using 1.3-diphenylisobenzofuran as a probe. The singlet oxygen quantum yields (ΦΔ) for ZnPc loaded chitosan nanocapsules were high and similar to that of the standard (ZnPc in DMSO), displaying excellent ability to generate (1)O2. The photosensitizer loaded nanocapsules are photostable in the timescale usually utilized in PDT and only a small photobleaching event was observed when a light dose of 610J/cm(2) was applied. The in vitro drug release studies of ZnPc from all nanocapsules demonstrated a sustained release profile controlled by diffusion, without burst effect. The nature of the polymer and the core type of the nanocapsules regulated ZnPc release. Thus, the nanocapsules developed in this work are a promising strategy to be employed in PDT.

  2. Development of an Inhaled Sustained Release Dry Powder Formulation of Salbutamol Sulphate, an Antiasthmatic Drug

    PubMed Central

    Kumaresan, C.; Sathishkumar, K.

    2016-01-01

    The present research was aimed to develop and characterize a sustained release dry powder inhalable formulation of salbutamol sulphate. The salbutamol sulphate microparticles were prepared by solvent evaporation method using biodegradable polymer poly (D,L-lactic-co-glycolic acid) to produce salbutamol sulphate microparticle mixed with carrier respirable grade lactose for oral inhalation of dry powder. The drug content were estimated to produce 1 mg sustained release salbutamol sulphate per dose. Total four formulations K1, K2, K3 and K4 were prepared with 1:1, 1:2, 1:3, 1:4 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid). The developed formulations were studied for physicochemical properties, in vitro drug relase and Anderson cascade impaction studies. The prepared formulations effectively releases drug for 12 h in diffusion bag studies. Based on dissolution performance the 1:1 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid) produces in vitro release 92.57% at 12 h and having particle size of microparticles (D0.5μm) 5.02±0.6 and the pulmonary deposition of dry powder 34.5±3.21 (respiratory fraction in percentage). PMID:27168692

  3. Grafting of graphene oxide with stimuli-responsive polymers by using ATRP for drug release

    NASA Astrophysics Data System (ADS)

    Zhu, Shenmin; Li, Jingbo; Chen, Yuhang; Chen, Zhixin; Chen, Chenxin; Li, Yao; Cui, Zhaowen; Zhang, Di

    2012-09-01

    A thermo-responsive drug delivery system was reported based on grafting of stimuli-responsive poly( N-isopropylacrylamide) (PNIPA) on the surface of graphene oxide (GO) via atom transfer radical polymerization. The successful synthesis of PNIPA attached on GO (GO-PNIPA) was confirmed by X-ray photoelectron spectrum, X-ray diffraction, atomic force microscope, field-emission scanning electron microscopy, and transmission electron microscopy measurements. Control of drug release through the composite GO-PNIPA was performed by measuring the uptake and release of ibuprofen (IBU). It was found the delivery system demonstrated a much high IBU storage of 280 wt%, attributing to the formation of the hydrogen bonding between the polymers on the GO surface and IBU as well as the large number of internal cavities of the PNIPA chains. In vitro test of IBU release exhibited a narrow pronounced transition at around 22 °C, indicating an attractive thermo-sensitive release property of this delivery system. The strategy may pave the way for the use of GO in numerous applications, from drug delivery to thermally responsive micro- and nano-devices.

  4. Toxins and adverse drug reactions affecting the equine nervous system.

    PubMed

    Dawson, Dominic R

    2011-12-01

    This article provides an overview of the more common toxins and adverse drug reactions, along with more rare toxins and reactions (Table 1), that result in neurologic dysfunction in horses. A wide variety of symptoms, treatments, and outcomes are seen with toxic neurologic disease in horses. An in-depth history and thorough physical examination are needed to determine if a toxin or adverse drug reaction is responsible for the clinical signs. Once a toxin or adverse drug reaction is identified, the specific antidote, if available, and supportive care should be administered promptly.

  5. Sustained release of a water-soluble drug from alginate matrix tablets prepared by wet granulation method.

    PubMed

    Mandal, Sanchita; Basu, Sanat Kumar; Sa, Biswanath

    2009-01-01

    Alginate matrix tablet of diltiazem hydrochloride (DTZ), a water-soluble drug, was prepared using sodium alginate (SAL) and calcium gluconate (CG) by the conventional wet granulation method for sustained release of the drug. The effect of formulation variables like SAL/CG ratio, drug load, microenvironmental pH modulator, and processing variable like compression force on the extent of drug release was examined. The tablets prepared with 1:2 w/w ratio of SAL/CG produced the most sustained release of the drug extending up to 13.5 h. Above and below this ratio, the drug release was faster. The drug load and the hardness of the tablets produced minimal variation in drug release. The addition of alkaline or acidic microenvironmental modulators did not extend the release; instead, these excipients produced somewhat faster release of diltiazem. This study revealed that proper selection of SAL/CG ratio is important to produce alginate matrix tablet by wet granulation method for sustained release of DTZ.

  6. Degradation and drug release of phosphate glass/polycaprolactone biological composites for hard-tissue regeneration.

    PubMed

    Kim, Hae-Won; Lee, Eun-Jung; Jun, In-Kook; Kim, Hyoun-Ee; Knowles, Jonathan C

    2005-10-01

    Phosphate-based glass (P-glass) and poly(epsilon-caprolactone) (PCL) composites were fabricated in a sheet form by solvent extraction and thermal pressing methods, and the antibiotic drug Vancomycin was loaded within the composites for use as a hard-tissue regenerative. The degradation and drug-release rate of the composites in vitro were tailored by modifying the glass composition: 0.45 P(2)O(5)-x CaO-(0.55-x)Na(2)O, where x=0.2, 0.3, 0.4, and 0.5. Compared to pure PCL, all the P-glass/PCL composites degraded to a higher degree, and the composite with lower-CaO glass showed a higher material loss. This was attributed mainly to the dissolution of the glass component. The glass dissolution also increased the degradation of PCL component in the composites. The Vancomycin release from the composites was strongly dependent on the glass composition. Drug release in pure PCL was initially abrupt and flattened out over a prolonged period. However, glass/PCL composites (particularly in the glass containing higher-CaO) exhibited a reduced initial burst and a higher release rate later. Preliminary cell tests on the extracts from the glass/PCL composites showed favorable cell proliferation, but the level was dependent on the ionic concentration of the extracts. The cell proliferation on the diluted extracts from the composite with higher-CaO glass was significantly higher than that on the blank culture dish. These observations confirmed that the P-glass/PCL composites are potentially applicable for use as hard-tissue regeneration and wound-healing materials because of their controlled degradation and drug-release profile as well as enhanced cell viability.

  7. Technetium-99m-labeled nanofibrillar cellulose hydrogel for in vivo drug release.

    PubMed

    Laurén, Patrick; Lou, Yan-Ru; Raki, Mari; Urtti, Arto; Bergström, Kim; Yliperttula, Marjo

    2014-12-18

    Nanoscale celluloses have recently gained an increasing interest in modern medicine. In this study, we investigated the properties of plant derived nanofibrillar cellulose (NFC) as an injectable drug releasing hydrogel in vivo. We demonstrated a reliable and efficient method of technetium-99m-NFC labeling, which enables us to trace the in vivo localization of the hydrogel. The release and distribution of study compounds from the NFC hydrogel after subcutaneous injection in the pelvic region of BALB/c mice were examined with a multimodality imaging device SPECT/CT. The drug release profiles were simulated by 1-compartmental models of Phoenix® WinNonlin®. The NFC hydrogel remained intact at the injection site during the study. The study compounds are more concentrated at the injection site when administered with the NFC hydrogel compared with saline solutions. In addition, the NFC hydrogel reduced the elimination rate of a large compound, technetium-99m-labeled human serum albumin by 2 folds, but did not alter the release rate of a small compound (123)I-β-CIT (a cocaine analogue). In conclusion, the NFC hydrogels is easily prepared and readily injected, and it has potential use as a matrix for controlled release or local delivery of large compounds. The interactions between NFC and specific therapeutic compounds are possible and should be investigated further.

  8. Surface characterization and drug release from porous microparticles based on methacrylic monomers and xanthan.

    PubMed

    Lungan, Maria-Andreea; Popa, Marcel; Racovita, Stefania; Hitruc, Gabriela; Doroftei, Florica; Desbrieres, Jacques; Vasiliu, Silvia

    2015-07-10

    Porous crosslinked microparticles based on glycidyl methacrylate and xanthan were prepared by suspension polymerization and used for loading theophylline, a bronhodilatator drug, in order to obtain new drug delivery systems. The surface morphologies observed by means of SEM and AFM analysis demonstrated that microparticles show a spherical shape and are characterized by a porous structure. The presence of xanthan in the structure of microparticles leads to a decrease of surface roughness and pore diameters as well as to an increase of hydrophilicity degree compared to the micropaticles based only on glycidyl methacrylate. To analyze the in vitro release data various mathematical models were used, such as, first order, Higuchi model, Korsmeyer-Peppas model and Baker-Lonsdale model. Based on the highest values of the correlation coefficient, the analysis of the kinetic data indicate that drug release from G1 and X1 porous microparticles fits similarly well to the first order and Higuchi models and diffusion was the dominant mechanism of drug release.

  9. Controlled release of oral tetrahydrocurcumin from a novel self-emulsifying floating drug delivery system (SEFDDS).

    PubMed

    Setthacheewakul, Saipin; Kedjinda, Wichan; Maneenuan, Duangkhae; Wiwattanapatapee, Ruedeekorn

    2011-03-01

    The objectives of this study were to develop and evaluate a novel self-emulsifying floating drug delivery system (SEFDDS) that resulted in improved solubility, dissolution, and controlled release of the poorly water-soluble tetrahydrocurcumin (THC). The formulations of liquid self-emulsifying drug delivery system (SEDDS; mixtures of Labrasol, Cremophor EL, Capryol 90, Labrafac PG) were optimized by solubility assay and pseudo-ternary phase diagram analysis. The liquid SEDDS was mixed with adsorbent (silicon dioxide), glyceryl behenate, pregelatinized starch, sodium starch glycolate, and microcrystalline cellulose and transformed into pellets by the extrusion/spheronization technique. The resulting pellets with 22% liquid SEDDS had a uniform size and good self-emulsification property. The microemulsions in aqueous media of different self-emulsifying floating pellet formulations were in a particle size range of 25.9-32.5 nm. Use of different weight proportions of glyceryl behenate and sodium starch glycolate in pellet formulations had different effects on the floating abilities and in vitro drug release. The optimum formulation (F2) had a floating efficiency of 93% at 6 h and provided a controlled release of THC over an 8-h period. The release rate and extent of release of THC liquid SEDDS (80% within 2 h) and self-emulsifying floating pellet formulation (80% within 8 h) were significantly higher than that of unformulated THC (only 30% within 8 h). The pellet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. Controlled release from this novel SEFDDS can be a useful alternative for the strategic development of oral solid lipid-based formulations.

  10. FACTORS AFFECTING THE DEPOSITION OF INHALED POROUS DRUG PARTICLES

    EPA Science Inventory

    Abstract
    Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol ...

  11. Local bacteria affect the efficacy of chemotherapeutic drugs

    PubMed Central

    Lehouritis, Panos; Cummins, Joanne; Stanton, Michael; Murphy, Carola T.; McCarthy, Florence O.; Reid, Gregor; Urbaniak, Camilla; Byrne, William L.; Tangney, Mark

    2015-01-01

    In this study, the potential effects of bacteria on the efficacy of frequently used chemotherapies was examined. Bacteria and cancer cell lines were examined in vitro and in vivo for changes in the efficacy of cancer cell killing mediated by chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was found to be significantly inhibited by certain bacteria, while the same bacteria improved the efficacy of six others. HPLC and mass spectrometry analyses of sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated modification of drug chemical structure. The chemoresistance or increased cytotoxicity observed in vitro with sample drugs (gemcitabine and CB1954) was replicated in in vivo murine subcutaneous tumour models. These findings suggest that bacterial presence in the body due to systemic or local infection may influence tumour responses or off-target toxicity during chemotherapy. PMID:26416623

  12. Histamine-releasing and allergenic properties of opioid analgesic drugs: resolving the two.

    PubMed

    Baldo, B A; Pham, N H

    2012-03-01

    Opioid analgesics are amongst the most commonly administered drugs in hospitals. Whether natural or synthetic, they show some common structural features, morphine-like pharmacological action and binding specificity for complementary opioid receptors. Tramadol differs from the other opioid analgesics in possessing monoaminergic activity in addition to its affinity for the µ opioid receptor. Many opioids are potent histamine releasers producing a variety of haemodynamic changes and anaphylactoid reactions, but the relationship of the appearance of these effects to the histamine plasma concentration is complex and there is no direct and invariable relationship between the two. Studies of the histamine-releasing effects, chiefly centred on morphine, reveal variable findings and conclusions often due to a range of factors including differences in technical measurements, dose, mode of administration, site of injection, the anatomical distribution of histamine receptors and heterogeneity of patient responses. Morphine itself has multiple direct effects on the vasculature and other haemodynamically-active mediators released along with histamine contribute to the variable responses to opioid drug administration. Despite their heavy use and occasional apparent anaphylactic-like side-effects, immunoglobulin E antibody-mediated immediate hypersensitivity reactions to the drugs are not often encountered. Uncertainties associated with skin testing with these known histamine-releasers, and the general unavailability of opioid drug-specific immunoglobulin E antibody tests contribute to the frequent failure to adequately investigate and establish underlying mechanisms of reactions by distinguishing anaphylactoid from true anaphylactic reactions. Clinical implications for diagnosis of reactions and some speculations on the rarity of true Type 1 allergies to these drugs are presented.

  13. Prenatal Drug Exposure Affects Neonatal Brain Functional Connectivity

    PubMed Central

    Salzwedel, Andrew P.; Vachet, Clement; Gerig, Guido; Lin, Weili

    2015-01-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala–frontal, insula–frontal, and insula–sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala–frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention. PMID:25855194

  14. Preparation of a novel chitosan-microcapsules/starch blend film and the study of its drug-release mechanism.

    PubMed

    Huo, Weiqiang; Xie, Gancheng; Zhang, Weixin; Wang, Wei; Shan, Junyang; Liu, Hechou; Zhou, Xiaohua

    2016-06-01

    A novel drug delivery system, chitosan-microcapsules/starch blend film for antofloxacin controlled release, was prepared, and characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (X-RD), thermogravimetry and derivative thermogravimetry (TG/DTG), and scanning electron microscopy (SEM). Following incorporation of the chitosan-microcapsules in the film matrix, the synergistic interactions between these drug-carriers were significant. The thermostability and mechanical properties of the blend film were greatly improved by the incorporation of the microcapsules. The water resistance of the blend film was enhanced by increasing the content of microcapsules, indicating that the microcapsules acted as moisture barriers. After being incorporated, chitosan-microcapsules/starch blend film shows a sustained drug release. The extent of the film degradation and microcapsules swelling in the release system indicated that the drug released of the blend film was pH-sensitive. The blend film exhibited pharmacodynamic efficacy because of the efficient drug releasing.

  15. Ca-carboxymethyl xanthan gum mini-matrices: Swelling, erosion and their impact on drug release mechanism.

    PubMed

    Maity, Siddhartha; Sa, Biswanath

    2014-07-01

    The effect of Ca(2+) ion concentration on swelling, erosion, and drug release mechanism of Ca(2+) ion cross-linked carboxymethyl xanthan gum (Ca-CMXG) matrices was investigated. By adding CaCl2 solution, carboxymethyl xanthan gum (CMXG) was converted into Ca-CMXG matrix, which was evaluated for swelling, erosion and drug release in different dissolution media. The amount of Ca(2+) ion alters the viscosity of gel layer formed around the matrices resulting in decreased water penetration into swollen layer. The changes in amount of Ca(2+) ion considerably influenced the swelling and erosion of the matrix leading to different drug release profiles. The simultaneous swelling and erosion of matrices that were controlled by the degree of cross-linking prejudiced the drug release mechanism. The release data fitted well into the Korsmeyer-Peppas equation and the combined effect of diffusion and erosion described the overall drug transport mechanism.

  16. The Role of Acoustic Cavitation in Ultrasound-triggered Drug Release from Echogenic Liposomes

    NASA Astrophysics Data System (ADS)

    Kopechek, Jonathan A.

    Cardiovascular disease (CVD) is the leading cause of death in the United States and globally. CVD-related mortality, including coronary heart disease, heart failure, or stroke, generally occurs due to atherosclerosis, a condition in which plaques build up within arterial walls, potentially causing blockage or rupture. Targeted therapies are needed to achieve more effective treatments. Echogenic liposomes (ELIP), which consist of a lipid membrane surrounding an aqueous core, have been developed to encapsulate a therapeutic agent and/or gas bubbles for targeted delivery and ultrasound image enhancement. Under certain conditions ultrasound can cause nonlinear bubble growth and collapse, known as "cavitation." Cavitation activity has been associated with enhanced drug delivery across cellular membranes. However, the mechanisms of ultrasound-mediated drug release from ELIP have not been previously investigated. Thus, the objective of this dissertation is to elucidate the role of acoustic cavitation in ultrasound-mediated drug release from ELIP. To determine the acoustic and physical properties of ELIP, the frequency-dependent attenuation and backscatter coefficients were measured between 3 and 30 MHz. The results were compared to a theoretical model by measuring the ELIP size distribution in order to determine properties of the lipid membrane. It was found that ELIP have a broad size distribution and can provide enhanced ultrasound image contrast across a broad range of clinically-relevant frequencies. Calcein, a hydrophilic fluorescent dye, and papaverine, a lipophilic vasodilator, were separately encapsulated in ELIP and exposed to color Doppler ultrasound pulses from a clinical diagnostic ultrasound scanner in a flow system. Spectrophotometric techniques (fluorescence and absorbance measurements) were used to detect calcein or papaverine release. As a positive control, Triton X-100 (a non-ionic detergent) was added to ELIP samples not exposed to ultrasound in order

  17. The pH-controlled dual-drug release from mesoporous bioactive glass/polypeptide graft copolymer nanomicelle composites.

    PubMed

    Xia, Wei; Chang, Jiang; Lin, Jiaping; Zhu, Jianqi

    2008-06-01

    Dual-drug delivery systems are investigated for combined therapy with drugs having distinct therapeutic effects. However, the majority of current dual-drug delivery systems are designed for simultaneous release of two different drugs; the release of each individual drug cannot be controlled. In this study, we have demonstrated a novel dual-drug delivery system based on mesoporous bioactive glass/polypeptide graft copolymer nanomicelle composites. Water-soluble gentamicin and fat-soluble naproxen were used as model drugs in the study of this system. A pH-controlled release of individual drugs was achieved by the predominant release of gentamicin from mesoporous bioactive glass in an acid environment and fast release of naproxen in an alkaline environment from polypeptide nanomicelles. Our results suggest that the mesoporous bioactive glass/PBLG-g-PEG nanomicelle composites can be used as a dual-drug delivery system, and that the individual drug release can be controlled by the pH of the surrounding environment.

  18. Effect of drug physicochemical properties on swelling/deswelling kinetics and pulsatile drug release from thermoresponsive poly(N-isopropylacrylamide) hydrogels.

    PubMed

    Coughlan, D C; Quilty, F P; Corrigan, O I

    2004-07-23

    The effect of drug physicochemical properties on swelling/deswelling kinetics and pulsatile drug release from a thermoresponsive hydrogel was examined. Hydrogels were loaded with drug and thermally triggered swelling/deswelling and release experiments were performed. Two series of drugs of contrasting hydrophilicity and varying physicochemical properties were examined. Benzoic acid (BA), its methyl and propyl esters, and diltiazem base were used as model hydrophobic drugs. Sodium benzoate (NaB), diltiazem HCl (DHCl), vitamin B12 (VB12) and various dextrans (MW 4300, 10,200, 42,000, 68,800) were used as model hydrophilic agents of increasing size. The hydrogel swelling rate was slowed by the presence of the hydrophobic drugs and this decreased rate was solubility dependant for the benzoates. The hydrophilic series increased the rate of swelling compared to the unloaded system. In all cases, the magnitude and rate of hydrogel contraction were proportional to the extent of swelling prior to temperature switch. Drug release was by diffusion below the lower critical solution temperature (LCST), while a solubility-dependent drug pulse release on temperature switch was observed for the hydrophobic series. Effectiveness of thermal control of hydrophobic drug release increased with increasing solubility. The hydrophilic series produced a molecular size-dependent drug pulse on temperature switch above the LCST. Pulsatile on-off drug release was shown with DHCl, VB12 and the various dextrans. Drug solubility, size and chemical nature were shown to be of particular importance in the control of hydrogel swelling and drug release from thermosensitive hydrogels.

  19. Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways

    SciTech Connect

    Vickers, Alison E.M.; Heale, Jason; Sinclair, John R.; Morris, Stephen; Rowe, Josh M.; Fisher, Robyn L.

    2012-04-01

    Drug induced thyroid effects were evaluated in organotypic models utilizing either a rat thyroid lobe or human thyroid slices to compare rodent and human response. An inhibition of thyroid peroxidase (TPO) function led to a perturbation in the expression of key genes in thyroid hormone synthesis and release pathways. The clinically used thiourea drugs, methimazole (MMI) and 6-n-propyl-2-thioruacil (PTU), were used to evaluate thyroid drug response in these models. Inhibition of TPO occurred early as shown in rat thyroid lobes (2 h) and was sustained in both rat (24–48 h) and human (24 h) with ≥ 10 μM MMI. Thyroid from rats treated with single doses of MMI (30–1000 mg/kg) exhibited sustained TPO inhibition at 48 h. The MMI in vivo thyroid concentrations were comparable to the culture concentrations (∼ 15–84 μM), thus demonstrating a close correlation between in vivo and ex vivo thyroid effects. A compensatory response to TPO inhibition was demonstrated in the rat thyroid lobe with significant up-regulation of genes involved in the pathway of thyroid hormone synthesis (Tpo, Dio1, Slc5a5, Tg, Tshr) and the megalin release pathway (Lrp2) by 24 h with MMI (≥ 10 μM) and PTU (100 μM). Similarly, thyroid from the rat in vivo study exhibited an up-regulation of Dio1, Slc5a5, Lrp2, and Tshr. In human thyroid slices, there were few gene expression changes (Slc5a5, ∼ 2-fold) and only at higher MMI concentrations (≥ 1500 μM, 24 h). Extended exposure (48 h) resulted in up-regulation of Tpo, Dio1 and Lrp2, along with Slc5a5 and Tshr. In summary, TPO was inhibited by similar MMI concentrations in rat and human tissue, however an increased sensitivity to drug treatment in rat is indicated by the up-regulation of thyroid hormone synthesis and release gene pathways at concentrations found not to affect human tissue. -- Highlights: ► Novel model of rat thyroid or human thyroid slices to evaluate pathways of injury. ► TPO inhibition by MMI or PTU altered

  20. Evidence to suggest that gonadotropin-releasing hormone inhibits its own secretion by affecting hypothalamic amino acid neurotransmitter release.

    PubMed

    Feleder, C; Jarry, H; Leonhardt, S; Moguilevsky, J A; Wuttke, W

    1996-10-01

    The mediobasal hypothalamus of rats contains gonadotropin-releasing hormone (GnRH) receptors. These hypothalamic neurons also express the GnRH corresponding gene. Under these circumstances, the possibility exists that these GnRH receptors could be localized in other neurons, which are GnRH-receptive, unknowing the neurotransmitter quality. Therefore, we studied the in vitro effects of the GnRH agonist buserelin on GnRH, glutamate, gamma-amino-butyric acid (GABA) and taurine release from explanted superfused hypothalami of untreated and buserelin-pretreated (down-regulated) male rats. When buserelin was added to the superfusion medium it inhibited promptly the release of GnRH and the excitatory amino acid neurotransmitter glutamate, but stimulated the release of the inhibitory neurotransmitters, GABA and taurine. Hypothalamic release of GnRH from hypothalami collected from buserelin-treated (30 micrograms/100 g b.w. twice daily for 4 days) male rats released significantly less GnRH, glutamate and more GABA and taurine. The inhibitory effect of buserelin was maintained when the superfusion medium continuously contained the GnRH analog. When superfusion of hypothalami from buserelin-pretreated animals was performed in the absence of buserelin, GnRH and glutamate release increased significantly within 45-60 min, whereas GABA and taurine release decreased at this time point. When buserelin was added to the superfusion medium 2 h after buserelin-free superfusion, GnRH and glutamate release decreased whereas GABA and taurine release increased instantaneously. Buserelin-treated rats showed significantly low values of LH and testosterone than the untreated rats. These results suggest that GnRH receptors may not only be present in GnRH axon terminals in the median eminence, but also on glutamatergic, GABAergic and taurinergic neurons by which GnRH may exert an autoinhibitory ultrashort loop feedback on its own secretion. This effect appears to be connected with glutamatergic

  1. Multifunctional yolk-in-shell nanoparticles for pH-triggered drug release and imaging

    PubMed Central

    Chen, Hongyu; Qi, Bin; Moore, Thomas; Wang, Fenglin; Colvin, Daniel C.; Sanjeewa, Liurukara D.; Gore, John C.; Hwu, Shiou-Jyh; Mefford, O. Thompson; Alexis, Frank; Anker, Jeffrey N.

    2015-01-01

    Multifunctional nanoparticles are synthesized for both pH-triggered drug release and imaging with radioluminescence, upconversion luminescent, and magnetic resonance imaging (MRI). The particles have a yolk-in-shell morphology, with a radioluminescent core, an upconverting shell, and a hollow region between the core and shell for loading drugs. They are synthesized by controlled encapsulation of a radioluminescent nanophosphor yolk in a silica shell, partial etching of the yolk in acid, and encapsulation of the silica with an upconverting luminescent shell. Metroxantrone, a chemotherapy drug, was loaded into the hollow space between X-ray phosphor yolk and up-conversion phosphor shell through pores in the shell. To encapsulate the drug and control the release rate, the nanoparticles are coated with pH-responsive biocompatible polyelectrolyte layers of charged hyaluronic acid sodium salt and chitosan. The nanophosphors display bright luminescence under X-ray, blue light (480 nm), and infrared light (980 nm). They also served as T1 and T2 MRI contrast agents with relaxivities of 3.5 mM−1 s−1 (r1) and 64 mM−1s−1 (r2). These multifunctional nanocapsules have applications in controlled drug delivery and multimodal imaging. PMID:24753264

  2. Hydrophobic polymers modification of mesoporous silica with large pore size for drug release

    NASA Astrophysics Data System (ADS)

    Zhu, Shenmin; Zhang, Di; Yang, Na

    2009-04-01

    Mesostructure cellular foam (MCF) materials were modified with hydrophobic polyisoprene (PI) through free radical polymerization in the pores network, and the resulting materials (MCF-PI) were investigated as matrices for drug storage. The successful synthesis of PI inside MCF was characterized by Fourier transform infrared (FT-IR), hydrogen nuclear magnetic resonance (1H NMR), X-ray diffraction patterns (XRD) and nitrogen adsorption/desorption measurements. It was interesting to find the resultant system held a relatively large pore size (19.5 nm) and pore volume (1.02 cm3 g-1), which would benefit for drug storage. Ibuprofen (IBU) and vancomycin were selected as model drugs and loaded onto unmodified MCF and modified MCF (MCF-PI). The adsorption capacities of these model drugs on MCF-PI were observed increase as compared to that of on pure MCF, due to the trap effects induced by polyisoprene chains inside the pores. The delivery system of MCF-PI was found to be more favorable for the adsorption of IBU (31 wt%, IBU/silica), possibly attributing to the hydrophobic interaction between IBU and PI formed on the internal surface of MCF matrix. The release of drug through the porous network was investigated by measuring uptake and release of IBU.

  3. A Review of Preclinical Research Demonstrating that Drug and Non-Drug Reinforcers Differentially Affect Behavior

    PubMed Central

    Kearns, David N.; Gomez-Serrano, Maria A.; Tunstall, Brendan J.

    2013-01-01

    This review describes and summarizes current preclinical research revealing important differences between drug and non-drug reinforcers in terms of their effects on behavior. Despite research showing that drugs are not especially strong reinforcers in animals, a number of other behavioral differences potentially relevant to addiction have been reported in studies that have compared drug and non-drug reinforcers. Several of these effects appear only after long-term access to drugs. These include an escalation of drug intake, an increased persistence in responding for the drug, and a decreased sensitivity to the effects of punishers or other suppressors of drug seeking. Further differences between drug and non-drug reinforcers include the effects that reinforcer-paired stimuli have on behavior. Drug cues, as compared to food cues, have been shown to exert greater control over reinforcer-seeking behavior after periods of abstinence. Similarly, behavior previously reinforced by drugs, but not food, has been shown to be susceptible to stress-induced reinstatement after extinction. The behavioral differences between drug and non-drug reinforcers reviewed here may identify special features of drugs that lead to addiction. PMID:21999697

  4. Swelling and drug release behavior of poly(2-hydroxyethyl methacrylate/itaconic acid) copolymeric hydrogels obtained by gamma irradiation

    NASA Astrophysics Data System (ADS)

    Tomić, S. Lj.; Mićić, M. M.; Filipović, J. M.; Suljovrujić, E. H.

    2007-05-01

    The new copolymeric hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) were prepared by gamma irradiation, in order to examine the potential use of these hydrogels in controlled drug release systems. The influence of IA content in the gel on the swelling characteristics and the releasing behavior of hydrogels, and the effect of different drugs, theophylline (TPH) and fenethylline hydrochloride (FE), on the releasing behavior of P(HEMA/IA) matrix were investigated in vitro. The diffusion exponents for swelling and drug release indicate that the mechanisms of buffer uptake and drug release are governed by Fickian diffusion. The swelling kinetics and, therefore, the release rate depends on the matrix swelling degree. The drug release was faster for copolymeric hydrogels with a higher content of itaconic acid. Furthermore, the drug release for TPH as model drug was faster due to a smaller molecular size and a weaker interaction of the TPH molecules with(in) the P(HEMA/IA) copolymeric networks.

  5. The effect of HPMC particle size on the drug release rate and the percolation threshold in extended-release mini-tablets.

    PubMed

    Mohamed, Faiezah A A; Roberts, Matthew; Seton, Linda; Ford, James L; Levina, Marina; Rajabi-Siahboomi, Ali R

    2015-01-01

    The particle size of HPMC is a critical factor that can influence drug release rate from hydrophilic matrix systems. Percolation theory is a statistical tool which is used to study the disorder of particles in a lattice of a sample. The percolation threshold is the point at which a component is dominant in a cluster resulting in significant changes in drug release rates. Mini-tablets are compact dosage forms of 1.5-4 mm diameter, which have potential benefits in the delivery of drug to some patient groups such as pediatrics. In this study, the effect of HPMC particle size on hydrocortisone release and its associated percolation threshold for mini-tablets and tablets was assessed. For both mini-tablets and tablets, large polymer particles reduced tensile strength, but increased the drug release rate and the percolation threshold. Upon hydration, compacts with 45-125 μm HPMC particles formed a strong gel layer with low porosity, reducing hydrocortisone release rates. In comparison, faster drug release rates were obtained when 125-355 µm HPMC particles were used, due to the greater pore sizes that resulted in the formation of a weaker gel. Using 125-355 µm HPMC particles increased the percolation threshold for tablets and to a greater extent for mini-tablets. This work has demonstrated the importance of HPMC particle size in ER matrices, the effects of which are even more obvious for mini-tablets.

  6. Study on drug release of and biological response to UHMWPE wear debris carrying estradiol

    NASA Astrophysics Data System (ADS)

    Qu, Shuxin; Liu, Aiqin; Liu, Xiaomin; Bai, Yinlong; Weng, Jie

    2012-12-01

    The aim of this study is to investigate in vitro release of 17β-estradiol (E2), the potential drug to treat osteolysis, and the biological response to ultra-high molecular weight polyethylene loaded with E2 (UHMWPE-E2) wear debris. The osteoblasts (MC3T3-E1) and macrophages (RAW264.7) were co-cultured with UHMWPE-E2 wear debris via inversion culture technique, respectively. MTT, ALP and ELISA assay were employed to evaluate the cell proliferation, ALP activity and the expression of interleukin-6 (IL-6). In vitro E2 release included: initial burst release, celerity release and steady release. The E2 released steadily after 40 d and lasted more than 60 d. The E2 in UHMWPE-E2 wear debris promoted the proliferation and ALP activity of MC3T3-E1 cells at the high debris dosages of 8-10 mg. In particular, the UHMWPE-E2 wear debris inhibited the expression of IL-6 of osteoblasts at all dosages in the present study. RAW264.7 cells cultured with UHMWPE-E2 and UHMWPE wear debris exhibited large sizes about 100 μm in diameter. The small size wear debris presented inside of cells indicated that the wear debris activated the phagocytosis of macrophages. The results indicated the E2 in UHMWPE-E2 would play a role in the treatment of the debris induced-osteolysis after artificial hip joint replacement.

  7. Effects of gonadotropin-releasing hormone administration or a controlled internal drug-releasing insert after timed artificial insemination on pregnancy rates of dairy cows

    PubMed Central

    Jeong, Jae Kwan; Choi, In Soo; Kang, Hyun Gu; Hur, Tai Young

    2016-01-01

    This study investigated the effects of gonadotrophin-releasing hormone (GnRH) administration (Experiment 1) and a controlled internal drug-releasing (CIDR) insert (Experiment 2) after timed artificial insemination (TAI) on the pregnancy rates of dairy cows. In Experiment 1, 569 dairy cows that underwent TAI (day 0) following short-term synchronization with prostaglandin F2α were randomly allocated into two groups: no further treatment (control, n = 307) or injection of 100 µg of gonadorelin on day 5 (GnRH, n = 262). In Experiment 2, 279 dairy cows that underwent TAI (day 0) following Ovsynch were randomly allocated into two groups: no further treatment (control, n = 140) or CIDR insert treatment from days 3.5 to 18 (CIDR, n = 139). The probability of pregnancy following TAI did not differ between the GnRH (34.4%) and control (31.6%, p > 0.05) groups. However, the probability of pregnancy following TAI was higher (odds ratio: 1.74, p < 0.05) in the CIDR group (51.1%) than in the control group (39.3%). Overall, CIDR insert treatment at days 3.5 to 18 increased pregnancy rates relative to non-treated controls, whereas a single GnRH administration on day 5 did not affect the pregnancy outcomes of dairy cows. PMID:27030200

  8. Electrospinning of drug-loaded polymer systems: preparation, characterization and drug release

    NASA Astrophysics Data System (ADS)

    Russo, Giuseppina; Vittoria, Vittoria; Lamberti, Gaetano; Titomanlio, Giuseppe

    2010-06-01

    In this paper we formulated and characterized biomedical devices for bone tissue regeneration. These systems were realized homogenously dispersing lamellar Hydrotalcite loaded with Diclofenac Sodium in a polymeric matrix of PCL (Poly-caprolactone). These biomedical devices were obtained through the electrospinning technique that has shown many advantages with respect to others techniques, in particular very interesting micro-fiber loaded with HDik were obtained. Drug delivery results were analyzed considering a mathematical modeling to evaluate the diffusivity coefficients.

  9. Silk fibroin/copolymer composite hydrogels for the controlled and sustained release of hydrophobic/hydrophilic drugs.

    PubMed

    Zhong, Tianyi; Jiang, Zhijuan; Wang, Peng; Bie, Shiyu; Zhang, Feng; Zuo, Baoqi

    2015-10-15

    In the present study, a composite system for the controlled and sustained release of hydrophobic/hydrophilic drugs is described. Composite hydrogels were prepared by blending silk fibroin (SF) with PLA-PEG-PLA copolymer under mild aqueous condition. Aspirin and indomethacin were incorporated into SF/Copolymer hydrogels as two model drugs with different water-solubility. The degradation of composite hydrogels during the drug release was mainly caused by the hydrolysis of copolymers. SF with stable β-sheet-rich structure was not easily degraded which maintained the mechanical integrity of composite hydrogel. The hydrophobic/hydrophilic interactions of copolymers with model drugs would significantly alter the morphological features of composite hydrogels. Various parameters such as drug load, concentration ratio, and composition of copolymer were considered in vitro drug release. Aspirin as a hydrophilic drug could be controlled release from composite hydrogel at a constant rate for 5 days. Its release was mainly driven by diffusion-based mechanism. Hydrophobic indomethacin could be encapsulated in copolymer nanoparticles distributing in the composite hydrogel. Its sustained release was mainly degradation controlled which could last up to two weeks. SF/Copolymer hydrogel has potential as a useful composite system widely applying for controlled and sustained release of various drugs.

  10. Size-Tunable and Functional Core-Shell Structured Silica Nanoparticles for Drug Release

    SciTech Connect

    Chi, Fangli; Guo, Ya Nan; Liu, Jun; Liu, Yunling; Huo, Qisheng

    2010-02-18

    Size-tunable silica cross-linked micellar core-shell nanoparticles (SCMCSNs) were successfully synthesized from a Pluronic nonionic surfactant (F127) template system with organic swelling agents such as 1,3,5-trimethylbenzene (TMB) and octanoic acid at room temperature. The size and morphology of SCMCSNs were directly evidenced by TEM imaging and DLS measurements (up to ~90 nm). Pyrene and coumarin 153 (C153) were used as fluorescent probe molecules to investigate the effect and location of swelling agent molecules. Papaverine as a model drug was used to measure the loading capacity and release property of nanoparticles. The swelling agents can enlarge the nanoparticle size and improve the drug loading capacity of nanoparticles. Moreover, the carboxylic acid group of fatty acid can adjust the release behavior of the nanoparticles.

  11. Bone cell activity responsive drug release from biodegradable apatite/collagen nano-composite cements--in vitro dissolution medium responsive vitamin K2 release.

    PubMed

    Otsuka, Makoto; Hirano, Ryuhei

    2011-07-01

    A biodegradable drug delivery system with perforated macro pores was established using an apatite/collagen composite cement containing menatetrenone (VK2). The drug-release capabilities of the device were investigated in vitro under osteoblast and osteoclast-like conditions (SOB and SOC). A bulk powder of apatite cement containing 2.5% VK2 and 20% bovine collagen was obtained by grinding, kneaded with phosphoric acid, and poured into molds, producing fixed blocks with 0-60 perforated macro pores. The characteristics of these samples were measured by X-ray powder diffraction analysis and Fourier-transformed and infrared spectroscopy, and found to be very similar to those of natural bone. Drug release tests were performed under SOB in simulated body fluid (pH 7.8), and then under SOC in acetate buffer (pH 4.5) at 37.0±0.1 °C, and the process repeated twice. The device released almost no drug in SOB, but a significant amount in SOC. The drug release in SOC was not proportional to the number of macro pores in the first test, but was in the second. The device showed dissolution medium-responsive drug release.

  12. Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan.

    PubMed

    Lim, S T; Martin, G P; Berry, D J; Brown, M B

    2000-05-15

    Rapid mucociliary clearance of intranasally administered drugs is often a key factor in determining the bioavailability of such therapeutic agents. The use of mucoadhesive microparticles provide a potential strategy for improving retention of drugs within the nasal cavity, and thereby improve the resultant pharmacokinetic profile. This study describes the comparison of a number of novel, potentially mucoadhesive microspheres, prepared by solvent evaporation, composed of hyaluronic acid (HA), chitosan glutamate (CH) and a combination of the two with microcapsules of HA and gelatin prepared by complex coacervation. The microspheres had a mean particle size of 19.91+/-1.57 microm (HA), 28.60+/-1.34 microm (HA/CH), 29.47+/-3.58 microm (CH). The incorporation of a model drug, gentamicin sulphate (%) was 46.90+/-0.53 (HA), 28.04+/-1.21 (HA/CH) and 13.32+/-1.04 (CH). The in vitro release profiles of microsphere formulations prepared by solvent evaporation were determined. The release of gentamicin from HA and HA/CH was 50% longer than CH and was best modelled as a release from a matrix. The degree of mucoadhesion of each formulation was investigated by determining the mucociliary transport rate (MTR) of the microparticles across an isolated frog palate. Acacia/gelatin microcapsules were used as a positive control. The rank order of mucoadhesion for the microspheres and the microparticles was HA=HA/CH>CH>HA/gelatin>CHins. The entrapment of gentamicin did not affect the mucoadhesive properties (P>0.05, Mann--Whitney U-test). The combination of HA with chitosan may afford additional advantages in combining the mucoadhesive potential of HA with the penetration enhancing effect of chitosan.

  13. Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery

    NASA Astrophysics Data System (ADS)

    Cao, Yanwu; Gao, Min; Chen, Chao; Fan, Aiping; Zhang, Ju; Kong, Deling; Wang, Zheng; Peer, Dan; Zhao, Yanjun

    2015-03-01

    Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic payloads are maximizing the therapeutic outcomes while minimizing adverse effects. Yet one of the major challenges facing drug developers is the dilemma of premature versus on-demand drug release, which influences the therapeutic regiment, efficacy and potential toxicity. Herein, we report on redox-sensitive polymer-drug conjugate micelles for on-demand intracellular delivery of a model active agent, curcumin. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a disulfide bond or ester bond (control), respectively. The self-assembled redox-sensitive micelles exhibited a hydrodynamic size of 115.6 ± 5.9 (nm) with a zeta potential of -10.6 ± 0.7 (mV). The critical micelle concentration was determined at 6.7 ± 0.4 (μg mL-1). Under sink conditions with a mimicked redox environment (10 mM dithiothreitol), the extent of curcumin release at 48 h from disulfide bond-linked micelles was nearly three times higher compared to the control micelles. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in HeLa cells at 18.5 ± 1.4 (μg mL-1), whereas the IC50 of control micelles was 41.0 ± 2.4 (μg mL-1). The cellular uptake study also revealed higher fluorescence intensity for redox-sensitive micelles. In conclusion, the redox-sensitive polymeric conjugate micelles could enhance curcumin delivery while avoiding premature release, and achieving on-demand release under the high glutathione concentration in the cell cytoplasm. This strategy opens new avenues for on-demand drug release of nanoscale intracellular delivery platforms that ultimately might be translated into pre-clinical and future clinical practice.

  14. Anticancer drug released from near IR-activated prodrug overcomes spatiotemporal limits of singlet oxygen.

    PubMed

    Rajaputra, Pallavi; Bio, Moses; Nkepang, Gregory; Thapa, Pritam; Woo, Sukyung; You, Youngjae

    2016-04-01

    Photodynamic therapy (PDT) is a cancer treatment modality where photosensitizer (PS) is activated by visible and near IR light to produce singlet oxygen ((1)O2). However, (1)O2 has a short lifetime (<40 ns) and cannot diffuse (<20 nm) beyond the cell diameter (e.g., ∼ 1800 nm). Thus, (1)O2 damage is both spatially and temporally limited and does not produce bystander effect. In a heterogeneous tumor, cells escaping (1)O2 damage can regrow after PDT treatment. To overcome these limitations, we developed a prodrug concept (PS-L-D) composed of a photosensitizer (PS), an anti-cancer drug (D), and an (1)O2-cleavable linker (L). Upon illumination of the prodrug, (1)O2 is generated, which damages the tumor and also releases anticancer drug. The locally released drug could cause spatially broader and temporally sustained damage, killing the surviving cancer cells after the PDT damage. In our previous report, we presented the superior activity of our prodrug of CA4 (combretastatin A-4), Pc-(L-CA4)2, compared to its non-cleavable analog, Pc-(NCL-CA4)2, that produced only PDT effects. Here, we provide clear evidence demonstrating that the released anticancer drug, CA4, indeed damages the surviving cancer cells over and beyond the spatial and temporal limits of (1)O2. In the limited light illumination experiment, cells in the entire well were killed due to the effect of released anti-cancer drug, whereas only a partial damage was observed in the pseudo-prodrug treated wells. A time-dependent cell survival study showed more cell death in the prodrug-treated cells due to the sustained damage by the released CA4. Cell cycle analysis and microscopic imaging data demonstrated the typical damage patterns by CA4 in the prodrug treated cells. A time-dependent histological study showed that prodrug-treated tumors lacked mitotic bodies, and the prodrug caused broader and sustained tumor size reduction compared to those seen in the tumors treated with the pseudo-prodrug. This data

  15. pH- and temperature-sensitive polymeric microspheres for drug delivery: the dissolution of copolymers modulates drug release.

    PubMed

    Fundueanu, Gheorghe; Constantin, Marieta; Stanciu, Cristina; Theodoridis, Georgios; Ascenzi, Paolo

    2009-12-01

    Most pH-/temperature-responsive polymers for controlled release of drugs are used as cross-linked hydrogels. However, the solubility properties of the l